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Preparation of Hierarchical Hollow CaCO3 Particles and the Application as Anticancer Drug Carrier
Abstract
One-pot approach to couple the crystallization of CaCO(3) nanoparticles and the in situ symmetry-breaking assembly of these crystallites into hollow spherical shells was developed under the templating effect of a soluble starch. Further functional study using HP-a as an anticancer drug carrier (DOX) demonstrated its advantages for localizing drug release by the pH value-sensitive structure and enhancing cytotoxicity by increasing cellular uptake, perinuclear accumulation, and nuclear entry.
... For example, the pore diameter of multilayer-modified PLGA (mPLGA) scaffold after the nano-HAPs mineralizing is reduced from 284.0 µm to 203.4 µm ( Figure 3A) [74]. Similar to nano-HAPs, the biocompatible CaCO 3 nanoparticles are occupied in an orderly way on the macroporous network skeleton structure of the mineralized carriers, and the mineralized layer is generated to fill some defects of the pore scaffold ( Figure 3B) [75]. The mineralized porous structure improves the compression strength of HAP-mPLGA scaffold by 10.78 times compared to the PLGA scaffold ( Figure 3C), while accelerating bone regeneration [74]. ...
... The pore morphology of nanohydroxyapatite particles (nano-HAPs) mineralized on the poly-(lactide-co-glycolide acid) (PLGA)before and after modification (A), and the compression strength, osteogeny differentiation and cell proliferation performances (C) of the poly-(lactide-coglycolide acid) porous scaffold before and after mineralization (Asterisks represent data with an error of less than 0.05, which is statistically significant.) (Reproduced with permission from ref.[74], copyright 2018, Wiley-VCH); and the ring-like mineralized growth of the porous CaCO3 in figures a-f (B) (reproduced with permission from ref.[75], copyright 2008, American Chemical Society). ...
... The pore morphology of nanohydroxyapatite particles (nano-HAPs) mineralized on the poly-(lactide-co-glycolide acid) (PLGA)before and after modification (A), and the compression strength, osteogeny differentiation and cell proliferation performances (C) of the poly-(lactide-coglycolide acid) porous scaffold before and after mineralization (Asterisks represent data with an error of less than 0.05, which is statistically significant.) (Reproduced with permission from ref.[74], copyright 2018, Wiley-VCH); and the ring-like mineralized growth of the porous CaCO 3 in figures a-f (B) (reproduced with permission from ref.[75], copyright 2008, American Chemical Society). ...
Porous structures with light weight and high mechanical performance exist widely in the tissues of animals and plants. Biomimetic materials with those porous structures have been well-developed, and their highly specific surfaces can be further used in functional integration. However, most porous structures in those tissues can hardly be entirely duplicated, and their complex structure-performance relationship may still be not fully understood. The key challenges in promoting the applications of biomimetic porous materials are to figure out the essential factors in hierarchical porous structures and to develop matched preparation methods to control those factors precisely. Hence, this article reviews the existing methods to prepare biomimetic porous structures. Then, the well-proved effects of micropores, mesopores, and macropores on their various properties are introduced, including mechanical, electric, magnetic, thermotics, acoustic, and chemical properties. The advantages and disadvantages of hierarchical porous structures and their preparation methods are deeply evaluated. Focusing on those disadvantages and aiming to improve the performance and functions, we summarize several modification strategies and discuss the possibility of replacing biomimetic porous structures with meta-structures.
... In the acidic environment of cancer cells, calcium carbonate loaded with anticancer drugs such as doxorubicin hydrochloride (DOX) can be released slowly. Wei et al. [32] prepared hollow calcium carbonate particles using starch as a template and used it as a carrier for the anticancer drug DOX. The results showed that the drug released from the carrier was pH-dependent, which could make the drug gather around the target cancer cell and enter the nucleus to enhance its toxicity to cancer cells. ...
... However, research by Yang et al. [33] shows that cancer cells have developed several possible resistance mechanisms, such as loss of T cell function β 2 microglobulin gene mutation, and changes in tumor target antigens, Apelin receptor (APLNR) gene mutation, intestinal flora imbalance, and so on. In order to obtain a better anti-cancer effect, the drug carrier prepared by Wei et al. [32] can directly invade the nucleus of cancer cells, but the process and mechanism of its entry into the nucleus are unclear. In addition to increasing uptake, these behaviors significantly improve the nuclear delivery efficiency of anticancer drugs and obtain better tumor cytotoxicity. ...
A drug carrier usually refers to a tool that can carry the effective ingredients of drugs into the human body. The drug-controlled release system prepared by a new drug carrier can allow the gradual release of the drug in the human body at a stable rate, thus decreasing the frequency of administration and reducing the toxicity and side effects thereof; however, existing drug carriers generally have problems such as low drug loading, poor biocompatibility, stability, and specificity, each of which could be improved. Calcium carbonate can be used as a sustained-release carrier of active substances, with good biocompatibility, biodegradability, low cost, easy preparation, and broad application prospects. This paper reviews the synthesis and structural characteristics of calcium carbonate carrier materials and the related research progress of calcium carbonate as a controlled release carrier for therapeutic drugs, providing a reference for promoting the research and application of calcium carbonate as a drug carrier.
... In contrast, spontaneous diffusion controlled release from soft alginate carriers [37]. The CaCO 3 -AH system formed a stable slow-release drug delivery platform in which CaCO 3 provided sufficient internal space and powerful attraction for the loading and storing drug molecules [38]. The CaCO 3 -AH carriers were shown capable of targeted drug delivery with sustained release. ...
... In contrast, spontaneous diffusion controlled release from soft alginate carriers [37]. The CaCO3-AH system formed a stable slow-release drug delivery platform in which CaCO3 provided sufficient internal space and powerful attraction for the loading and storing drug molecules [38]. The CaCO3-AH carriers were shown capable of targeted drug delivery with sustained release. ...
In this review, we aim to provide a summary of recent research advancements and applications of algin (i.e., alginic acid) and alginate-hybrid materials (AHMs) in medical fields. Algin/alginate are abundant natural products that are chemically inert and biocompatible, and they have superior gelation properties, good mechanical strengths, and biodegradability. The AHMs have been widely applied in wound dressing, cell culture, tissue engineering, and drug delivery. However, medical applications in different fields require different properties in the AHMs. The drug delivery application requires AHMs to provide optimal drug loading, controlled and targeted drug-releasing, and/or visually guided drug delivery. AHMs for wound dressing application need to have improved mechanical properties, hydrophilicity, cell adhesion, and antibacterial properties. AHMs for tissue engineering need improved mechanical properties that match the target organs, superior cell affinity, and cell loading capacity. Various methods to produce AHMs that meet different needs were summarized. Formulations to form AHMs with improved stability, drug/cell-loading capacity, cell adhesion, and mechanical properties are active research areas. This review serves as a road map to provide insights into the strategies to develop AHMs in medical applications.
... 2,3,6 Another widely-studied inorganic material is calcium carbonate, which is low cost, safe, accessible, biocompatible, bioresorptive and osteoconductive. 7,8 Calcium carbonate has three crystalline polymorphs, namely calcite, aragonite and vaterite. 9,10 The differences in the morphological forms of calcium carbonate may be related to their synthetic conditions. ...
... It is well documented that HA and calcium carbonate, used either alone or combined, have demonstrated osteogenicity and bone conductivity. 1,4,7,8,15 In the present study, HA/aragonite supported ALP activity of mesenchymal stem cells in vitro, which is a sign of enhanced osteogenicity. ...
A self-hardening three-dimensional (3D)-porous composite bone graft consisting of 65 wt% hydroxyapatite (HA) and 35 wt% aragonite was fabricated using a 3D-Bioplotter®. New tetracalcium phosphate and dicalcium phosphate anhydrous/aragonite/gelatine paste formulae were developed to overcome the phase separation of the liquid and solid components. The mechanical properties, porosity, height and width stability of the end products were optimised through a systematic analysis of the fabrication processing parameters including printing pressure, printing speed and distance between strands. The resulting 3D-printed bone graft was confirmed to be a mixture of HA and aragonite by X-ray diffraction, Fourier transform infrared spectroscopy and energy dispersive X-ray spectroscopy. The compression strength of HA/aragonite was between 0.56 and 2.49 MPa. Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro. The osteogenicity of HA/aragonite was evaluated in vitro by alkaline phosphatase assay using human umbilical cord matrix mesenchymal stem cells, and in vivo by juxtapositional implantation between the tibia and the anterior tibialis muscle in rats. The results showed that the scaffold was not toxic and supported osteogenic differentiation in vitro. HA/aragonite stimulated new bone formation that bridged host bone and intramuscular implants in vivo. We conclude that HA/aragonite is a biodegradable and conductive bone formation biomaterial that stimulates bone regeneration. Since this material is formed near 37°C, it will have great potential for incorporating bioactive molecules to suit personalised application; however, further study of its biodegradation and osteogenic capacity is warranted. The study was approved by the Animal Ethical Committee at Tongji Medical School, Huazhong University of Science and Technology (IACUC No. 738) on October 1, 2017.
... 16 They are used as abrasives and absorbents in cosmetics, and as therapeutic drug carriers. [17][18][19] However, their application, depends on their morphology, crystal form, size and surface properties. [20][21][22][23] Although small CaCO 3 particles can be obtained from natural sources by comminution, they are rarely monodispersed or impurity free. ...
CaCO3 particles grow excessively upon chemical precipitation in the absence of impurities or growth inhibitors. Additive Ca2+ ions have been shown to preferentially adsorb on CaCO3 precipitates, effectively inhibiting their growth and promoting the crystallization of pure calcite without an observable intermediate phase. This phenomenon can be adapted towards the synthesis of small calcite particles from a conventional chemical precipitation method. Complementing such effort, this study discusses the influence of additive Ca2+ ions concentration and solution pH on the extent of CaCO3 growth inhibition. Equal volumes of equimolar CaCl2 and Na2CO3 solutions were mixed in a tubular reactor at a constant flowrate. The precipitates were continuously dispersed in Ca(OH)2 solution, where Ca2+ ions irreversibly adsorb on their surfaces. Compared to conditions where additive Ca2+ ions are absent, this method can produce more than 90% decrease in particle size. The results show the degree of growth inhibition increases as the concentration of additive Ca2+ ions increase. However, it is limited by increasing volume of precipitates. This study also reveals an unusual role of media pH. Here, growth inhibition that leads to the synthesis of monodisperse submicron CaCO3 particles is only observed in high alkaline pH conditions. This is due to the hydration of additive Ca2+ ions in low pH conditions. While additive Ca2+ ions adsorb on CaCO3 precipitates in pH conditions above the isoelectric point (pH ≈ 9), their ability to limit CaCO3 growth diminishes when pH < 12.
... This provides insight for previous experimental observations: (1) proteins destined to reach the nucleus often form complexes before translocating to the nucleus, 44,45 (2) attaching specific moieties to anticancer drug particles, thereby increasing their size, facilitates targeting to the ER, 46,47 and (3) different types of particles, such as lipid and CaCO3 nanoparticles, whose sizes are larger than typical proteins, 22 tend to accumulate in the perinuclear region. [12][13][14] While we focused on proteins with sizes comparable to the ER width ($20 nm), cells also contain significantly larger particles ([20 nm) like vesicles and lysosomes. 48,49 These extremely large particles might interact with actin filaments, whose mesh size is approximately 50 nm. ...
All proteins are translated in the cytoplasm, yet many, including transcription factors, play vital roles in the nucleus. While previous research has concentrated on molecular motors for the transport of these proteins to the nucleus, recent observations reveal perinuclear accumulation even in the absence of an energy source, hinting at alternative mechanisms. Here, we propose that structural properties of the cellular environment, specifically the endoplasmic reticulum (ER), can promote molecular transport to the perinucleus without requiring additional energy expenditure. Specifically, physical interaction between proteins and the ER impedes their diffusion and leads to their accumulation near the nucleus. This result explains why larger proteins, more frequently interacting with the ER membrane, tend to accumulate at the perinucleus. Interestingly, such diffusion in a heterogeneous environment follows Chapman’s law rather than the popular Fick’s law. Our findings suggest a novel protein transport mechanism arising solely from characteristics of the intracellular environment.
... Nanoparticle-based carriers have become the common materials of research at Nanomedicine application because they allow loading drugs and control the dose of used drugs Therefore, they are promising for medicine and bio-application [1][2][3][4][5][6][7][8]. Graphene oxide with unique properties and two-dimensional flaky sheets with excellent physical, chemical and biological properties were first reported in 2004 [9,10]. ...
... A moderately smooth surface is noticed. Spherical nanoparticles show up on the surfaces of hydrogel matrices in Fig. 4 (b) is due to the presence of CaCO 3 /SiO 2 nanocomposite [23,30,33]. ...
... Furthermore, vaterite has been proposed as a coating pigment for inkjet paper, owing to its advantageous properties such as easy and cost-effective preparation, the ability to design particles with defined characteristics, a porous structure, mild conditions for decomposition, non-toxicity, and biocompatibility. The continuous synthesis of submicron calcium carbonate particles has been a subject of intense research due to its wide-ranging applications in various industries, including pharmaceuticals, cosmetics, and materials science [2][3][4][5]. However, the achievement of precise control over the size, morphology, and porosity of these particles has posed a significant challenge. ...
The challenge of continuous CaCO3 particle synthesis is addressed using microfluidic technology. A custom microfluidic chip was used to synthesize CaCO3 nanoparticles in vaterite form. Our focus revolved around exploring one-phase and two-phase synthesis methods tailored for the crystallization of these nanoparticles. The combination of scanning electron microscopy, X-ray diffraction, dynamic light scattering, and small-angle scattering allowed for an evaluation of the synthesis efficiency, including the particle size distribution, morphology, and polymorph composition. The results demonstrated the superior performance of the two-phase system when precipitation occurred inside emulsion microreactors, providing improved size control compared with the one-phase approach. We also discussed insights into particle size changes during the transition from one-phase to two-phase synthesis. The ability to obtain CaCO3 nanoparticles in the desired polymorph form (∼50 nm in size, 86–99% vaterite phase) with the possibility of scaling up the synthesis will open up opportunities for various industrial applications of the developed two-phase microfluidic method.
... An expert approach was used to build the cognitive map using simple calculation procedures and expert analysis of the content of the identified publications. In the literature on the subject, there are more and more examples of using this tool to diagnose various types of phenomena, including modeling [28][29][30], knowledge management [31,32], political and social issues [33], engineering and technology management [29], agriculture and ecological modeling [30], management [34], forecasting [35,36], medical decision support and classification tasks [30,37], and sustainable financial systems [30,38]. ...
Sustainability is understood as a balanced integration of economic, ecological, and social aspects. Sustainable manufacturing can be considered one of the most important issues to address in the pursuit of sustainable development. The main purpose of the paper is to identify the most important directions of research to date and to indicate new and emerging areas of research concerned with the usage of decision-making methods in sustainability assessment in steel manufacturing companies. A systematic review was based on the publications indexed in the Web of Science and Scopus databases. In the analysis, the correspondence analysis and log-linear model were applied. To sum up, this study examines decision-making modalities and sustainable performance in terms of approaches that influence sustainability in steel manufacturing. Firstly, the study determined key decision-making aspects, such as the appropriate material identification for the manufacturing process and material labeling for the manufacturing process, which is essential for sustainable metal products. Secondly, the identification of sustainability indicators is considered vital in the hierarchical process as their integration is essential for the decision-making process and its outcome. Furthermore, system efficiency and productivity, alongside increasing attention to environmental protection, have led to significant changes in all production systems. In addition, many factors play an important role in the selection of suppliers, such as increasing the importance of the environment, increasing the recycling rate of the products, and ensuring sustainability performance. However, companies in the steel manufacturing industry rely little on the application of decision-making to assess sustainability.
... CaCO 3 has medical applications in modern healthcare systems, which has also attracted the interest of researchers all over the world. It is an appropriate filler in terms of the environment because it is less polluting, less toxic [47,48], affordable and biocompatible as well [49][50][51]. ...
Nanotechnology has facilitated unique ways of developing novel nano-composites. In that sense, polymer-based nano-composites are being extensively researched for their outstanding properties as a result of incorporating nano-fillers in the polymer matrix. They have activated enormous research interests owing to their potential in addressing environmental issues, packaging, optics, electronics, battery electrolytes, pneumatic actuation, molecular separations, sensors, biomedical applications, etc. Hence, the authors intend to consolidate reported information about these polymer matrices, diverse inorganic nanofillers, and nano-filled polymer composites for improvement in properties and future advanced applications. The review exhaustively covers 15 years of literature on theoretical, experimental, and application aspects of PVA & PMMA-based nano-composites. It also summarizes the structure-property correlations that govern their performance. Hence this review is hoped to provide the readers with stimulating insights on strategies, noteworthy challenges, and future opportunities/prospects in developing polymer nano-composites that may cater to the need of our society and scientific industries as well.
... The drug-CaCO 3 hybrids can be established by the passivate adsorption of drug (macro)molecular compounds on mineral surfaces, and therefore, the relatively weak binding strength in between may cause inadequate sustained release or targeting. The nanosized CaCO 3 particles [2][3][4], porous CaCO 3 scaffolds [5][6][7][8], mesocrystals [9], and hollow microparticles [10,11] featured by large surface areas become promising candidates for high drug load and efficient release performance. Nevertheless, the synthetic routes to these CaCO 3 -drug composite particles can be sophisticated and require strict experimental conditions. ...
Extensive exploration is required to deploy mineralization as a tool to develop low-cost yet efficient sustained drug release systems. Unlike previous studies which directly incorporated drug components in mineralized products, we propose an emerging approach to synthesizing drug-loaded CaCO3 composites, relying on the synergistic occlusion of the molecular solutions comprising both the alginate hydrogel matrices and the associated drug (doxorubicin) in the course of mineralization. Independent tools including a scanning electron microscope and adsorption isotherm were employed to characterize the lyophilized composites, which led to the conclusion that the anticancer drug doxorubicin (DOX) was uniformly dispersed in the hydrogel matrices as a molecular solution. The occlusion strategy led to CaCO3-based composites with high loads and sustained and pH-responsive release of DOX. Considering many drug molecules can form molecular solutions with polymeric components, we find that the synergistic occlusion can become a general approach to designing smart drug delivery systems.
... In order to prevent DOX leakage and heighten cellular uptake, DOX@GdMSNs were coated with TSLs containing folic acid (FA). In response to near-infrared (NIR) irradiation, ICG generated heat and ruptured ICG-TSLs, releasing DOX efficiently [62]. Needless to say, MSNs' potential for site-specific targeting is likely to boost cancer treatment efficacy, owing to their imaging capabilities. ...
Inorganic nanocarriers are potent candidates for delivering conventional anticancer drugs, nucleic acid-based therapeutics, and imaging agents, influencing their blood half-lives, tumor targetability, and bioactivity. In addition to the high surface area-to-volume ratio, they exhibit excellent scalability in synthesis, controllable shape and size, facile surface modification, inertness, stability, and unique optical and magnetic properties. However, only a limited number of inorganic nanocarriers have been so far approved for clinical applications due to burst drug release, poor target specificity, and toxicity. To overcome these barriers, understanding the principles involved in loading therapeutic and imaging molecules into these nanoparticles (NPs) and the strategies employed in enhancing sustainability and targetability of the resultant complexes and ensuring the release of the payloads in extracellular and intracellular compartments of the target site is of paramount importance. Therefore, we will shed light on various loading mechanisms harnessed for different inorganic NPs, particularly involving physical entrapment into porous/hollow nanostructures, ionic interactions with native and surface-modified NPs, covalent bonding to surface-functionalized nanomaterials, hydrophobic binding, affinity-based interactions, and intercalation through co-precipitation or anion exchange reaction.
... Nano-and micro-particles of calcium carbonate (CaCO 3 ), an important material, have been widely used in many fields, such as the construction industry, paper industry, cosmetics, toothpastes, water treatment, pigments, and drug delivery systems [42,43]. The synthesis of CaCO 3 has attracted many researchers' interests in recent years because of its good properties, such as the high ratio of surface area to volume, high porosity, nontoxicity and compatibility toward the human body [44]. ...
Background
Climate change caused by greenhouse gas emission has become a global hot topic. Although biotechnology is considered as an environmentally friendly method to produce chemicals, almost all biochemicals face carbon dioxide emission from inevitable respiration and energy metabolism of most microorganisms. To cater for the broad prospect of biochemicals, bioprocess optimization of diverse valuable products is becoming increasingly important for environmental sustainability and cleaner production. Based on Ca(OH) 2 as a CO 2 capture agent and pH regulator, a bioprocess was proposed for co-production of 1,3-propanediol (1,3-PDO), biohydrogen and micro-nano CaCO 3 by Clostridium butyricum DL07.
Results
In fed-batch fermentation, the maximum concentration of 1,3-PDO reached up to 88.6 g/L with an overall productivity of 5.54 g/L/h. This productivity is 31.9% higher than the highest value previously reports (4.20 g/L/h). In addition, the ratio of H 2 to CO 2 in exhaust gas showed a remarkable 152-fold increase in the 5 M Ca(OH) 2 group compared to 5 M NaOH as the CO 2 capture agent. Green hydrogen in exhaust gas ranged between 17.2% and 20.2%, with the remainder being N 2 with negligible CO 2 emissions. During CO 2 capture in situ, micro-nano calcite particles of CaCO 3 with sizes in the range of 300 nm to 20 µm were formed simultaneously. Moreover, when compared with 5M NaOH group, the concentrations of soluble salts and proteins in the fermentation broth of 5 M Ca(OH) 2 group were notably reduced by 53.6% and 44.1%, respectively. The remarkable reduction of soluble salts and proteins would contribute to the separation of 1,3-PDO.
Conclusions
Ca(OH) 2 was used as a CO 2 capture agent and pH regulator in this study to promote the production of 1,3-PDO. Meanwhile, micro-nano CaCO 3 and green H 2 were co-produced. In addition, the soluble salts and proteins in the fermentation broth were significantly reduced.
Graphical Abstract
... [182,183] This study shows that the "dual-action" (i.e., cell-microdrilling and drug release) of biogenic hybrid micromotors potentially achieve single-cell target precision of noninvasive surgery together with the additional advantage of the drug release property to act as a package of "drug-rehabilitating cellular microsurgery." Calcified porous microneedles (40-60 µm long) extracted from Dracaena marginata [184,185] possess drug carrier capabilities (potentially calcium-based drug carriers), [186,187] and are coated with a magnetic layer to facilitate microdrilling by external magnetic actuation. It should be noted that such calcified biotubes are present in several plant species, scattered among both photosynthetic and nonphotosynthetic plant tissues under specialized cells termed idioblasts. ...
Plants are anatomically and physiologically different from humans and animals; however, there are several possibilities to utilize the unique structures and physiological systems of plants and adapt them to new emerging technologies through a strategic biomimetic approach. Moreover, plants provide safe and sustainable results that can potentially solve the problem of mass‐producing practical materials with hazardous and toxic side effects, particularly in the biomedical field, which requires high biocompatibility. In this review, it is investigated how micro–nanostructures available in plants (e.g., nanoparticles, nanofibers and their composites, nanoporous materials, and natural micromotors) are adapted and utilized in the design of suitable materials for a micro–nanorobot platform. How plants’ work on micro‐ and nanoscale systems (e.g., surface roughness, osmotically induced movements such as nastic and tropic, and energy conversion and harvesting) that are unique to plants, can provide functionality on the platform and become further prospective resources are examined. Furthermore, implementation across organisms and fields, which is promising for future practical applications of the plant‐actuated micro–nanorobot platform, especially on biomedical applications, is discussed. Finally, the challenges following its implementation in the micro–nanorobot platform are also presented to provide advanced adaptation in the future.
... In addition to such properties as biocompatibility, degradability, and low-toxicity, possessing a controllable porosity, hollow structure, and high surface areas is essential for efficient drug delivery carriers, since they can provide sufficient internal spaces and powerful attraction forces for the loading and storage of drug molecules [69]. To achieve the loading of drug molecules into CCPs, two methods can be adapted: physical adsorption and co-precipitation. ...
Because free therapeutic drug molecules often have adverse effects on normal tissues, deliver scanty drug concentrations and exhibit a potentially low efficacy at pathological sites, various drug carriers have been developed for preclinical and clinical trials. Their physicochemical and toxicological properties are the subject of extensive research. Inorganic calcium carbonate particles are promising candidates as drug delivery carriers owning to their hardness, porous internal structure, high surface area, distinctive pH-sensitivity, low degradability, etc, while soft organic alginate hydrogels are also widely used because of their special advantages such as a high hydration, bio-adhesiveness, and non-antigenicity. Here, we review these two distinct substances as well as hybrid structures encompassing both types of carriers. Methods of their synthesis, fundamental properties and mechanisms of formation, and their respective applications are described. Furthermore, we summarize and compare similarities versus differences taking into account unique advantages and disadvantages of these drug delivery carriers. Moreover, rational combination of both carrier types due to their performance complementarity (yin-&yang properties: in general, yin is referred to for definiteness as hard, and yang is broadly taken as soft) is proposed to be used in the so-called hybrid carriers endowing them with even more advanced properties envisioned to be attractive for designing new drug delivery systems.
... We believe our research findings along with a hypothetical schema we presented for the chitin-templated formation of calcite in I. basta could illuminate a broader understanding of the biomineralization process. Calcite, as one of the most widespread biominerals of nature, already has numerous known applications in biomedicine [54][55][56], civil engineering, and environmental sciences [57]. Relatedly, the discovery of the chitin-templated calcification process in I. basta demosponge as a renewable source of unique network-like scaffolds could bring another dimension to the applicability and reproducibility of calcium-based biomaterials in similar applications. ...
Marine sponges were among the first multicellular organisms on our planet and have survived to this day thanks to their unique mechanisms of chemical defense and the specific design of their skeletons, which have been optimized over millions of years of evolution to effectively inhabit the aquatic environment. In this work, we carried out studies to elucidate the nature and nanostructural organization of three-dimensional skeletal microfibers of the giant marine demosponge Ianthella basta, the body of which is a micro-reticular, durable structure that determines the ideal filtration function of this organism. For the first time, using the battery of analytical tools including three-dimensional micro—X-ray Fluorescence (3D-µXRF), X-ray diffraction (XRD), infra-red (FTIR), Raman and Near Edge X-ray Fine Structure (NEXAFS) spectroscopy, we have shown that biomineral calcite is responsible for nano-tuning the skeletal fibers of this sponge species. This is the first report on the presence of a calcitic mineral phase in representatives of verongiid sponges which belong to the class Demospongiae. Our experimental data suggest a possible role for structural amino polysaccharide chitin as a template for calcification. Our study suggests further experiments to elucidate both the origin of calcium carbonate inside the skeleton of this sponge and the mechanisms of biomineralization in the surface layers of chitin microfibers saturated with bromotyrosines, which have effective antimicrobial properties and are responsible for the chemical defense of this organism. The discovery of the calcified phase in the chitinous template of I. basta skeleton is expected to broaden the knowledge in biomineralization science where the calcium carbonate is regarded as a valuable material for applications in biomedicine, environmental science, and even in civil engineering.
In this study, we investigate the aggregation dynamics of colloidal silica by generating simulated structures and comparing them to experimental data gathered through scanning transmission electron microscopy (STEM). More specifically, diffusion-limited cluster aggregation and reaction-limited cluster aggregation models with different functions for the probability of particles sticking upon contact were used. Aside from using a constant sticking probability, the sticking probability was allowed to depend on the masses of the colliding clusters and on the number of particles close to the collision between clusters. The different models of the sticking probability were evaluated based on the goodness-of-fit of spatial summary statistics. Furthermore, the models were compared to the experimental data by calculating the structures’ fractal dimension and mass transport properties from simulations of flow and diffusion. The sticking probability, depending on the interaction with multiple particles close to the collision site, led to structures most similar to the STEM data.
Implant-associated infections and the increasing number of bone implants loosening and falling off after implantation have become urgent global challenges, hence the need for intelligent alternative solutions to combat implant loosening and falling off. The application of polyetheretherketone (PEEK) in biomedical and medical therapy has aroused great interest, especially because its elastic modulus close to bone provides an effective alternative to titanium implants, thereby preventing the possibility of bone implants loosening and falling off due to the mismatch of elastic modulus. In this Review, we provide a comprehensive overview of recent advances in surface modifications to prevent bone binding deficiency and bacterial infection after implantation of bone implants, starting with inorganics for surface modification, followed by organics that can effectively promote bone integration and antimicrobial action. In addition, surface modifications derived from cells and related products of biological activity have been proposed, and there is increasing evidence of clinical potential. Finally, the advantages and future challenges of surface strategies against medical associated poor osseointegration and infection are discussed, with promising prospects for developing novel osseointegration and antimicrobial PEEK materials.
Comprehensive Summary
Hierarchically porous materials (HP materials) are believed one of the most hopeful matrix materials because of their distinctive multimodal pore structures and tremendous application potentials in the field of biomedicine. However, green and facile synthesis of hierarchically porous nanomaterials with beneficial water dispersibility and biocompatibility is still a great challenge. Herein, a novel biomimetic strategy is proposed to prepare the cell‐tailored double‐shelled HPCaCO 3 /CaF 2 hollow nanospheres under the mediation of yeast cells. The biomolecules derived from the secretion of yeast cells are used as conditioning and stabilizing agents to control the biosynthesis of the HPCaCO 3 /CaF 2 materials, which exhibit excellent water dispersibility and favorable biocompatibility. The double‐shelled CaCO 3 /CaF 2 nanospheres hold hierarchically porous structure and have abundant pore channel and large specific surface area, showing high drug‐loading and a prolonged drug sustainable release profile by the pore‐by‐pore diffusion pattern of the hierarchical pores. Otherwise, the HPCaCO 3 with pH‐sensitivity could controllably release drug doxorubicin hydrochloride (DOX) at the acidic tumor microenvironment. Both in vitro and in vivo results demonstrate that HPCaCO 3 /CaF 2 has the sustainable pH‐sensitive drug release property, showing an enhanced therapeutic effect. Summarily, this study provides a biomimetic strategy to synthesize the hierarchically porous double‐shelled hollow nanomaterials for applying in sustainable drug delivery system.
This work aims to develop an eco-sound nano-bio-hybrid sorbent using sustainable materials for sorptive elimination of congo red and phosphates from aquatic environment. An amphipathic biopolymer derivative, high DS guar gum benzoate (GGBN) was used for entrapment of as synthesized calcium carbonate nanoparticles using solvent diffusion nano-precipitation technique. Designer nano-biohybrids were developed upon experimenting with various materials stoichiometry. SEM, XRD and EDX studies confirmed near-uniform impregnation of rhombohedral calcium carbonate crystals throughout the biopolymer matrix. Average pore size distribution and surface area of final product Ca-GGBNC, were estimated from NDLFT and BET methods respectively. Analysis of adsorption findings acquired at study temperature 27 ± 2 °C showed that the maximum adsorption capacity of Ca-GGBNC recorded qmax, 333.33 mg/g for congo red azo dye and that for phosphate was at 500 mg/g. Adsorptive removal was noted and both components followed pseudo second order kinetics. Intra-particle diffusion kinetics investigation disclosed that the boundary layer effect was prominent and the adsorption rates were not solely directed by the diffusion stage. Activation energy, Ea was to be estimated using Arrhenius equation at 56.136 and 47.015 KJ/mol for congo red and phosphates respectively. The calculated thermodynamic parameters(ΔG°, ΔH°, and ΔS°) revealed the spontaneous, feasible and endothermic sorption process. Owing to active surface area, spherical size, functional moiety and porous network, antibacterial properties of nanobiohybrid were persistent and MIC against E. coli and S. aureus were recorded at 200 μg/mL and 350 μg/mL respectively.
Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca²⁺-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core–shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca²⁺ with an immune-regulating ability and CO2 with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.
The calcium carbonate (CaCO3) scale generated in water pipes and heat exchangers causes serious problems such as pipe blockage and corrosion. This study investigates the effect of the 4-to-10 μm-long and 350-to-700 nm centering-nucleus-wide ZnO tetrapod-like nanomaterials and polydimethylsiloxane composite (t-ZnO/PDMS) on deposition and polymorphism of CaCO3 crystals on the stainless-steel substrate. The results showed that the t-ZnO/PDMS coating inhibited CaCO3 depositions and represented an excellent antifouling coating. The weight-based inhibition efficiencies of CaCO3 deposition were up to 81.3% and 63.2% at 20 °C and 60 °C, respectively. The t-ZnO/PDMS coating also exhibited good inhibition in the presence of liquid flow. The inhibition is primarily because the very fine concave-convex microstructure of the t-ZnO/PDMS coated surface lowered the surface energy of the substrates, making it difficult for CaCO3 crystals to adhere to the surface. Also, metastable vaterite and aragonite precipitations were dominant in the t-ZnO/PDMS coated coupons at 20 °C and 60 °C, respectively, whereas the uncoated coupon exhibited calcite as the predominant polymorph in all the studied conditions. The t-ZnO/PDMS composite subject to the liquid flow made calcites distorted and framboidal vaterite aggregates, likely due to their mechanical effects. The inhibition of CaCO3 depositions is due to achieving hydrophobicity on substrate surfaces, changing preferential polymorph formation, and tailoring the morphology of the given polymorph by the t-ZnO/PDMS composite.
Nucleation at different temperature levels can provide quantitative insights into the energy barrier associated with sub‐molecular nuclei. The accurate calculation of nucleation rates, thermodynamics, and interfacial energy for extremely small nanoclusters (1−2 nm) remains a challenge at high temperatures. Here, , are computed to estimate the nucleation rate of ultra‐small CaCO 3 pre‐nucleation clusters (0.85 nm) from thermogravimetric analysis (TGA) experimental values in the temperature range from 555 to 795 K, by adopting the most accurate iterative iso‐conversional method and random nucleation dependent differential function , respectively. On the basis of these analyses, four mathematical models are presented for computing nucleation rates and interfacial energy (mJ m ⁻² variation with temperature and conversion for CaCO 3 prenucleation clusters. Furthermore, experimental validation is also carried out in order to assess the existence of nucleation in CaCO 3 pre‐nucleation clusters at high temperatures (500 °C) using X‐ray diffraction and experimental z (α) master plots. The TGA can be used to predict and understand nucleation rates for various nano systems.
Pancreatic cancer is a malignant disease with high mortality, and its systemic treatment strategy mainly focuses on chemotherapy. Yet, the overall prognosis of pancreatic cancer patients is still extremely poor with a low survival rate. Gemcitabine (GEM) is a widely used chemotherapeutic agent for the treatment of pancreatic cancer. However, GEM chemoresistance remains the major challenge. In this study, we prepared calcium carbonate nanoparticles (CaCO3 NPs) loaded with a nucleotide reductase inhibitor (Triapine) and GEM to suppress the GEM resistance of pancreatic cancer cells (PANC-1/GEM) and solve the problem of poor solubility of Triapine. CaCO3-GEM-Triapine NPs nano-formulations enhanced the therapeutic effect of GEM-based chemotherapy by inhibiting cancer cell proliferation, migration, and resistance to GEM using both 2D PANC-1/GEM cells and 3D tumor spheroids. The study indicated that CaCO3 NPs loaded with GEM and Triapine could provide an effective treatment option to overcome drug resistance in pancreatic cancer.
The lack of effective oral drug delivery systems to treat gastric ulcer is an urgent challenge in clinical practice. Herein, a gastric acid pH-responsive hydrogel of curcumin/sodium alginate/polyaspartic acid@CaCO3 (Cur/SA/PC) was developed for sustained release of Cur, exerting effective protection and treatment of gastric ulcers. The in vitro gelatinization properties and the corresponding gel characteristics of the SA/PC delivery system demonstrated the successful construction of the in situ hydrogel with uniform strength. The cellular uptake illustrated the successful uptake and sustained release of Cur. Besides, Cur effectively inhibited NLRP3-mediated pyroptosis both in vitro and in vivo, exhibited an excellent pro-healing effect by regulating the PI3K/Akt signaling pathway, and alleviated acetic acid-induced chronic gastric injury in rats. Moreover, the relative bioavailability of Cur in the SA/PC hydrogel could effectively increase in the pharmacokinetic study. Importantly, the protective barrier formed by the SA/PC hydrogel could effectively protect against alcohol-induced acute gastric ulcers in rats. Overall, the designed SA/PC oral delivery system is a promising strategy to overcome gastric barriers for oral drug delivery.
A concept of interfacial competitive reaction between biomineralization and alginate gelation at an all-aqueous single-emulsion droplet interface to prepare robust coconut-like capsules (inner hard wall and outer soft wall) is developed. The concept is further applied for enzyme immobilization with high encapsulation efficiency, enzyme loading, mass transfer coefficient, and recyclability. The thickness and swelling properties of the shell are simply tunable by a competitive reaction. Our platform may open a green, facile, and efficient way to prepare organic-inorganic hybrid sustainable materials with tailored compositions and structures.
The bacterial colonization of surfaces and subsequent biofilm formation are a great threat in medical therapy and clinical diagnosis. The complex internal structure and composition sets an enormous obstacle for the localization and removal of biofilms. In this study, we proposed a novel biofilm-targeted nanocontainer with successive responsive property toward pH and ATP for precise localization and simultaneous bacterial eradication, with an acidic and adenosine triphosphate (ATP)-rich microenvironment within biofilms, formed due to the accumulation of fatty acids and ATP in the three-dimensional enclosed structure, integrated as two successive indicators to improve the precision of biofilm identification and removal. The biofilm-targeted nanocontainer was composed of a ATP-responsive zeolitic imidazolate framework-90 (ZIF-90) core loaded with Rho 6G and doxorubicin hydrochloride (DOX) encapsulated in the pH-responsive amorphous calcium carbonate/poly(acrylic acid) (ACC/PAA) shell. In the presence of biofilms, the ACC/PAA shell and ZIF-90 core were successively degraded by the accumulated H+ and ATP within biofilms, resulting in the release of fluorescence indicators and antimicrobial agents. On the other hand, to meet the application requirements of different biofilm scenarios, the pH response ability of the nanocontainers could be adjusted by changing the metallic ions (Ni2+, Zn2+, and Cu2+) doped into the structure of the ACC/PAA shell. Owing to excellent water dispersion of the pH/ATP double-responsive ZIF-90@Zn-ACC/PAA nanocontainer, precise localization and simultaneous bacterial eradication was successfully realized via a simple spray process. The successive pH/ATP two-step unlocking processes endowed the nanocontainers high precision for localization and simultaneous eradication of biofilms, which made the proposed nanocontainers high promising in food safety and medical treatment.
To effectively treat the environmental pollution caused by discarded crab shell, chitin was extracted from discarded crab shells by a combined chemical and biological process. The chitin extraction waste liquid was used to culture bacteria to synthesize biogenic vaterite (BV). The mineral morphology and physico-chemical properties of BV were characterized, and the loading characteristics and adsorption mechanism of doxorubicin hydrochloride (DOX) were investigated. The results showed that chitin could be extracted from crab shells using a combination of chemical and biological methods, and the purity of the extracted chitin reached 89.79%; cultivation of Bacillus velezensis using extraction waste liquid can induce the synthesis of stable BV; the maximum drug loading of BV towards DOX was 447.58 mg/g and its adsorption behavior fitted the Freundlich model. The findings provide new information for the processing utilization of waste crab shells and the development of novel drug carriers.
Targeted and high throughput manufacture of crystalline biominerals with diverse morphologies is of importance, due to the significant impact of shape and texture on the material properties, while tunable morphosynthesis of crystalline is restrained by the proper ion transfer process during the reactive crystallization, and is commonly regulated using organic soluble additives. Herein, Janus membranes (JMs) are facilely produced for the continuous confined reactive crystallization of calcium carbonate. Fabricated JM simultaneously achieves rapid and uniform directional CO3²⁻ ions transfer in the aqueous solution through the straight, uniform nanoscale hydrophilic channels, and the interfacial reactive crystallization is generated with confined ion adsorption and gating effect at the hydrophobic side. Hollow CaCO3 microcomposites via JM system are continuously and directly synthesized in the aqueous system without any assisted organic solvent or polymer additive, which is green and highly efficient. In addition, the reversed ion transfer direction in JM can be ideally managed resulting in highly selective manufacturing of cube or sphere‐type microcomposites. This study provides a feasible route for the rapid production of advanced particle materials with tunable morphology, displaying great potential applications of JM in material engineering.
We explore CaCO3 mineralization via the addition of a Ca(OH)2 solution to branched polyethylenimine–CO2 (PEI-CO2) adduct solutions. The alkylammonium carbamate zwitterions (i.e., CO2-adducted linkages) in PEI-CO2 adducts can hydrolyze to release bicarbonate ions to form CaCO3 in situ; meanwhile, the zwitterions themselves transform into the polyamine structure of polyethylenimine (PEI). The PEI-CO2 polymer serves as both the CO2 source and template for vaterite CaCO3 nucleation and growth. A relatively low dosage of the Ca(OH)2 solution (e.g., at 9.2–37% stoichiometry) preserves enough CO2-adducted linkages in the templating PEI-based chains, allowing them to firmly adsorb onto the growing vaterite nanocrystallites, providing long-term vaterite phase and colloidal stability. The high molecular weight of the used PEIs (e.g., 10 k–25 k Da) strengthens the adsorption as well. The mesoporous structure, the dissolution in a weakly acidic environment (pH 6.5), the low cytotoxicity, the ease of endocytosis, and the presence of reactive PEI amino groups all make the obtained vaterite nanoparticles a versatile candidate for effective and acid-responsive drug delivery. This work highlights the multifunctionality of PEI-CO2 adducts for CaCO3 mineralization, serving as a CO2 source and vaterite template and providing the vaterite phase and colloid stability, as well as reactivity for further modification.
Herein, membrane-assisted reactive crystallization (MARC) with effective interfacial flow regimes was proposed to achieve the effective mass transfer control during reactive crystallization. Three tube-shell side solution systems (EtOH-H2O, Butanol-H2O and H2O-H2O) were chosen to form different flow regimes on the membrane surface, including the microscale liquid layer and the uniform droplets. The fundamental mechanisms of ‘rising and falling tide’ phenomenon, and flexible layer thickness control were uncovered. A force analysis model was established to illustrate the transition behavior of the droplet and liquid layer on the membrane surface. Molecular simulations additionally demonstrated that MARC implemented various ion diffusion conditions in different solution systems. Compared to the conventional reactive crystallization, MARC with multiple flow regimes can achieve effective control of CaCO3 crystal size ranging from 700 nm to 3 μm and obtain uniform size distribution (coefficient of variation <15.1%), which shed light on the advanced material manufacture with reactive crystallization process.
This study demonstrates a method to inhibit the growth of CaCO 3 and synthesize submicron particles in a chemical precipitation process, under ambient and high supersaturation conditions. Equimolar CaCl 2 and Na 2 CO 3 ...
Crystalline calcium carbonate (CaCO3) particles have opened exciting perspectives for the design of multifunctional drug carriers with precise control over their growth, size, shape, polymorph, and mesoporosity. These particles, with dimensions varying from 10 nm to several microns, are typically obtained by mixing salts of calcium and carbonate. In this chapter, we give an overview of the research progress on the synthesis and characterization of well-defined CaCO3 particles for biomedical applications, especially as delivery systems for various active substances.
In this work, we demonstrate that porous MgACC microspheres could be prepared in liposome solution containing zwitterionic and anionic lipids. We find that the lipid molecules incorporated into MgACC could be as high as 10 mass%. Because hydrophobic drugs are lipophilic, the porous MgACC has been exploited as the carriers of hydrophobic drugs. Using lecithin as the source of lipids and N‐(rhodamine‐6G)lactam‐ethylenediamine (R6GNCCN) as the model of hydrophobic drugs, the optimal loading capacity was found to be ca. 1.4 mass%. The release of R6GNCCN to a phosphate buffer at pH 7.4 was over 90% within 5 hr. The drug release profile could be attenuated by encapsulating the MgACC core by a CaP shell. Lipid vesicles are used to facilitate the incorporation of hydrophobic drugs into the porous microspheres of Mg‐stabilized amorphous calcium carbonate (MgACC). Upon the dissolution of MgACC in the solution, the release of the drug molecules is triggered.
In the present work, we investigated the influence of the pore structure of molybdic acid-immobilized silicaalumina hollow spheres on their activity towards acid-promoted hydrogen evolution from aqueous ammonia borane solution. To control the pore structure, a surfactant, cetyltrimetylammonium bromide, and a swelling agent, 1-dodecylamine, were used during the shell formation of the hollow spheres. The amount of surfactant and swelling agent were found to influence the amount of mesopores formed. Further, the crystallinity of the immobilized molybdic oxide species as well as the ratio of inactive mixed oxides of aluminum and molybdenum decreased with increasing amounts of the surfactant and swelling agent. The immobilized hollow spheres with the high dispersed molybdic oxide and the inactive mixed oxide ratio also exhibited high activity towards hydrogen evolution from aqueous ammonia borane solution. The crystallinity of molybdic oxide tended to decrease with a decrease in the amount of immobilized molybdic acid. Furthermore, the hollow spheres with low molybdic oxide content exhibited high activity towards hydrogen evolution.
Calcium carbonate (CaCO3) has been widely studied as a drug delivery system (DDS), but it still has some limitations in its clinical application in tumor chemotherapy, such as difficult industrialization, complex synthesis methods, time-consuming and labor-intensive, and low drug loading. Here, we developed an industrialized method for the simple, rapid and controllable synthesis of high drug-loaded vaterite hollow CaCO3 (VHC). The VHC was successfully prepared by adding L-Leucine (Leu) in the process of preparing CaCO3 in an industrial method. The effects of different reaction conditions on VHC were studied in detail, and a possible formation mechanism of VHC was proposed. As an industrially synthesized DDS, the VHC had low cytotoxicity and good biocompatibility, and had higher loading capacity (39.68%) and encapsulation efficiency (90.17%) for doxorubicin hydrochloride (DOX) due to the existence of hollow nano-cavity. Meanwhile, [email protected] showed good pH responsiveness, which can achieve sustained release of DOX. And, [email protected] could significantly inhibit tumor cells (cell inhibitory rate: 91.73%) and reduce the toxicity to normal cells. The high drug-loaded VHC synthesized rapidly by industrial methods can achieve controllable drug delivery and high-efficiency inhibition of tumor cells, and has a good application prospect in tumor therapy.
Bioreactor is a system where target substances could be generated through biochemical reaction or bioconversion by utilizing living conditions, including organisms, tissues, cells and enzymes. In recent years, many multifunctional drug delivery systems based on bioreactors have been developed for disease treatment and/or diagnosis, owing to their advantages of good biocompatibility, disease targeting ability, versatility, and low side effects. Therefore, it is essential to understand the basic principles and guidelines behind the designing of suitable bioreactor-based drug delivery systems, and also necessary to make a comprehensive summary of its cutting-edge research progress. In this review, we focus on the design principles and strategies of bioreactor-based drug delivery systems and summarize the advantages and applications from the aspects of in vivo bioreactors, cell-based bioreactors, and cellular vesicles-based bioreactors. In addition, we also highlight the applications of bioreactor-based drug delivery systems in the treatment or diagnosis of cancer, inflammatory bowel disease, Alzheimer's disease, and many other diseases. This review aims to serve as an up-to-date compilation in this area and provide inspiration for scientists in the field of biomedical applications.
In the present study, the SrCO3@montmorillonite nanocomposite was synthesized by loading Sr(NO3)2 on natural bentonite using a controlled and facile microwave method. The SrCO3@montmorillonite nanoparticles characteristics are identified using advanced techniques such as infrared spectroscopy (IR), energy‐dispersive X‐ray analysis (EDX), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and pore size distribution analysis. Crossed-aldol condensation of an aromatic aldehyde with cycloalkanone in the presence of these nanoparticles produced α, ά-bis(substituted-benzylidene) cycloalkanones in good yields without using any solvent. The present method is operationally simple and dosed not use organic solvent, which makes the process environmentally benign.
We report here on functionalization of surgical meshes (PVDF) with novel hybrid material, consisting of Ag@crown nanoparticles, embedded on CaCO3/PEG nanosheets. Nanosheets of PEG 4000 with average thickness of 25 nm enclosing CaCO3 nanoparticles with average sizes of 150 nm were applied for sustained release of Ag@crown nanoparticles that in turn serve as antibacterial agent. The characterization of obtained hybrid nanostructures was carried out by microscopic and spectroscopic methods. Microbiological tests confirmed the effectiveness of hybrid material, consisting of Ag@crown nanoparticles, embedded in CaCO3/PEG nanostructure, as an antibacterial coating for surgical meshes. This coating was applied to insure antibacterial properties of meshes against microorganism colonization, in order to significantly improve their action in typical applications.
As is well known to all, delivering drug precisely to the tumor site is beneficial to improve the antitumor effect. In this study, we reported mesoporous silica nanoparticles (MSNs) coated with dual-film of calcium carbonate (CaCO3) and lipid bilayer (denoted as [email protected]3@liposomes) innovatively which achieve sustained drug release effect anchored at tumor microenvironment and enhanced biocompatibility. The pH-sensitive CaCO3 film acted as a guide to cap the pore channels of MSNs allowed pH-triggered drug release when transporting into cancer cells. Furthermore, the [email protected]3 was capsuled by lipid bilayer to improve cellular uptake efficiency and biocompatibility in blood circulation. Morphology of nanoparticles was characterized by transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) to confirm that double films were coated successfully. Doxorubicin hydrochloride (DOX) was efficaciously loaded into mesoporous pores as a model drug with a high drug loading content of 28%, forming DOX-loaded [email protected]3@liposomes (DOX/[email protected]3@liposomes). Non-specific protein adsorption and homolysis test revealed enhanced biocompatibility. Drug release study in vitro showed DOX/[email protected]3@liposomes could delay to release DOX at pH 5.0 and avoid releasing at pH 7.4. In vitro and in vivo antitumor efficiency evaluation showed that DOX/[email protected]3@liposomes have a desirable inhibitory activity on tumor growth. Therefore, Dual-film coated MSNs could be a good candidate for an antitumor drug delivery system.
Circulating tumor cells (CTCs) have been recognized as significant research target for cancer prognosis and metastasis mechanism. Efficient and all‐subpopulations‐covered isolation and facile release of CTCs with good viability are pivotal for profound mechanism research and molecular profiling. However, integrated nanoplatform with these two functions is yet to be elucidated. Among existing release techniques including physical, biological, and chemical methods, acid responsive release of CTCs attracts intensive interests due to its straightforward and easily accessible feature. However, extra acidic substance seems indispensable so far, which poses potential hazard to the rare and susceptible CTCs. To address this challenge, polyelectrolyte functionalized CaCO3 coated magnetic nanocrystal clusters are developed as the nanoplatform for multi‐subpopulations isolation and pH‐sensitive release of CTCs. Only buffer solution components are needed rather than other acidic substance to provide mild acidic environment with pH value of 6.5, facilitate highly efficient release. Moreover, the bioefficacy of CTC capture and mild condition recovery is not compromised by formation of protein corona on the cell‐friendly nanoplatform. This nanoplatform exhibits good performance in both mimic blood samples and cancer patients’ clinical samples. For cancer prognosis and molecular profiling of the circulating tumor cells (CTCs), a novel biocompatible, protein corona interference resistant, and positively‐charged core‐shell inorganic nanocomposite Fe3O4@CaCO3 as a multifunctional nanoplatform to efficiently isolate the CTCs from the clinical blood and ascitic fluid samples and subsequently mild pH sensitive release with well‐maintained viability is developed.
The partial pressure of oxygen (pO2) and pH play critical roles in tumor biology and therapy. We report here the first combined, high-resolution (< or = 10 microns) measurements of interstitial pH and pO2 profiles between adjacent vessels in a human tumor xenograft, using fluorescence ratio imaging and phosphorescence quenching microscopy. We found (1) heterogeneity in shapes of pH and pO2 profiles; (2) a discordant relation between local pH profiles and corresponding pO2 profiles, yet a strong correlation between mean pH and pO2 profiles; (3) no correlation between perivascular pH/pO2 and nearest vessel blood flow; and (4) well-perfused tumor vessels that were hypoxic and, consequently, large hypoxic areas in the surrounding interstitium. Such multiparameter measurements of the in vivo microenvironment provide unique insights into biological processes in tumors and their response to treatment.
Regular arrays of topologically complex, millimeter-scale objects were prepared by self-assembly, with the shapes of the assembling
objects and the wettability of their surfaces determining the structure of the arrays. The system was composed of solid objects
floating at the interface between perfluorodecalin and water and interacting by lateral capillary forces; patterning of the
wettability of the surfaces of the objects directs these forces. Self-assembly results from minimization of the interfacial
free energy of the liquid-liquid interface. Calculations suggest that this strategy for self-assembly can be applied to objects
on a micrometer scale.
Self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder dots, wires, and light-emitting diodes, generated electrically functional, three-dimensional networks. The patterns of dots and wires controlled the structure of the networks formed; both parallel and serial connections were generated.
The limitations of cisplatin as an anticancer drug have stimulated the search for other antitumor-active platinum complexes with improved pharmacological properties. The two main goals in the search for new platinum anti-cancer agents are the reduction of the dose-limiting toxicities of cisplatin and the circumvention of cisplatin resistance. However, it should be pointed out that this has proven to be a difficult task. In fact, less than 1% of the thousand of platinum complexes tested for pre-clinical antitumor activity have entered clinical trials in the past 30 years. Nonetheless, right now, several new platinum complexes are in clinical trials, a proof of the continued belief that platinum complexes may still fulfil the needs for novel antitumor drugs. This review will focus on the three main innovative approaches found in the platinum anticancer-field, namely, (1) compounds with decreased reactivity against nucleophiles, (2) compounds with carrier ligands, and (3) compounds which bind differently to DNA as compared to cisplatin. In the latter class, special attention is paid to dinuclear and polinuclear platinum complexes.
The potential of carbon nanotubes as carriers and delivery vectors for anticancer drugs was investigated. Herein, we propose MWNT-doxorubicin supramolecular complexes that can be developed for cancer therapy. The formation of such complexes is evidenced by a sharp decrease in the intensity of the doxorubicin fluorescence spectrum and takes place via π-π interactions with the MWNT backbone. In addition, the structural characteristics of the CNT-doxorubicin complexes were examined by transmission electron microscopy and showed well dispersed pluronic wrapped MWNT but clustered MWNT-doxorubicin structures. Very interestingly the doxorubicinMWNT complexes exhibit enhanced cytotoxic activity compared to both doxorubicin alone and doxorubicin-pluronic complexes.
Self-assembly is the autonomous organization of components into patterns or structures without human intervention. Self-assembling processes are common throughout nature and technology. They involve components from the molecular (crystals) to the planetary (weather systems) scale and many different kinds of interactions. The concept of self-assembly is used increasingly in many disciplines, with a different flavor and emphasis in each.
Hunter and hunted is not only a principle of nature but is also found in host–guest systems. J. de Mendoza and co-workers describe in their Communication on page 198 ff. how a host molecule (a small calix[4]arene or cavitand) can itself become the “prey” for a larger host (a metallocavitand made from a calix[4]arene with [3,8]phenanthroline subunits linked through Re atoms). The cover picture shows the complexation of a cavitand (by P. Ballester) superimposed on an underwater picture at Cap Andritxol, Mallorca (by E. Botana).
CuO/Cu2O composite hollow microspheres with controlled diameter and composition were prepared without the addition of templates and additives by hydrothermal synthesis using Cu(CH3COO)2·H2O as a precursor. Increasing the precursor concentration from 0.02 to 0.2 M increased the diameter of the composite hollow microspheres from 500 nm to 5 μm. Moreover, the content of Cu2O in the composite hollow microspheres increased with increasing the reaction time or/and precursor concentration to produce a range of composite hollow microspheres with Cu2O contents from 20 to 80 wt %. A localized Ostwald ripening mechanism was proposed to account for the formation of CuO/Cu2O composite hollow microspheres. The photocatalytic activity experiment indicated that the prepared CuO/Cu2O composite hollow microspheres exhibited a higher photocatalytic activity for the photocatalytic decolorization of methyl orange aqueous solution under the visible-light illumination than the single phase CuO or Cu2O samples.
Two contrasting approaches, involving either polymer-mediated or fluoride-mediated self-transformation of amorphous solid particles, are described as general routes to the fabrication of hollow inorganic microspheres. Firstly, calcium carbonate and strontium tungstate hollow microspheres are fabricated in high yield using sodium poly(4-styrenesulfonate) as a stabilizing agent for the formation and subsequent transformation of amorphous primary particles. Transformation occurs with retention of the bulk morphology by localized Ostwald ripening, in which preferential dissolution of the particle interior is coupled to the deposition of a porous external shell of loosely packed nanocrystals. Secondly, the fabrication process is extended to relatively stable amorphous microspheres, such as TiO2 and SnO2, by increasing the surface reactivity of the solid precursor particles. For this, fluoride ions, in the form of NH4F and SnF2, are used to produce well-defined hollow spheroids of nanocrystalline TiO2 and SnO2, respectively. Our results suggest that the chemical self-transformation of precursor objects under morphologically invariant conditions could be of general applicability in the preparation of a wide range of nanoparticle-based hollow architectures for technological and biomedical applications.
Hollow tin dioxide (SnO2) microspheres were synthesized by the simple heat treatment of a mixture composed of tin(IV) tetrachloride pentahydrate (SnCl(4)center dot 5H(2)O) and resorcinol-formaldehyde gel (RF gel). Because hollow structures were formed during the heat treatment, the pre-formation of template and the adsorption of target precursor on template are unnecessary in the current method, leading to simplified synthetic procedures and facilitating mass production. Field-emission scanning electron microscopy (FE-SEM) images showed 1.7-2.5 mu m sized hollow spherical particles. Transmission electron microscopy (TEM) images showed that the produced spherical particles are composed of a hollow inner cavity and thin outer shell. When the hollow SnO2 microspheres were used as a lithium-battery anode, they exhibited extraordinarily high discharge capacities and coulombic efficiency. The reported synthetic procedure is straightforward and inexpensive, and consequently can be readily adopted to produce large quantities of hollow SnO2 microspheres. This straightforward approach can be extended for the synthesis of other hollow microspheres including those obtained from ZrO2 and ZrO2/CeO2 solid solutions.
We have synthesized uniform and highly crystalline magnetite nanoparticles from the reaction of iron salts in microemulsion nanoreactors. The particle size can be controlled from 2 nm to 10 nm by varying the relative concentrations of the iron salts, surfactant, and solvent. Transmission electron microscope images of the nanoparticles reveal that they are very uniform in size distribution. Structural characterization using X-ray diffraction and X-ray magnetic circular dichroism shows that the nanoparticles are magnetite. The magnetic characterization of the nanoparticles showed that they are superparamagnetic at room temperature. Using a similar synthetic procedure, we have been able to synthesize nanoparticles of several mixed metal ferrites including cobalt ferrite, manganese ferrite, nickel ferrite, and zinc ferrite.
Hollow silica and silica-polymer spheres with diameters between 720 and 1000 nanometers were fabricated by consecutively assembling
silica nanoparticles and polymer onto colloids and subsequently removing the templated colloid either by calcination or decomposition
upon exposure to solvents. Scanning and transmission electron microscopy images demonstrate that the wall thickness of the
hollow spheres can be readily controlled by varying the number of nanoparticle-polymer deposition cycles, and the size and
shape are determined by the morphology of the templating colloid. The hollow spheres produced are envisioned to have applications
in areas ranging from medicine to pharmaceutics to materials science.
This paper describes a strategy that combines physical templating and capillary forces to assemble monodispersed spherical colloids into uniform aggregates with well-controlled sizes, shapes, and structures. When an aqueous dispersion of colloidal particles was allowed to dewet from a solid surface that had been patterned with appropriate relief structures, the particles were trapped by the recessed regions and assembled into aggregates whose structures were determined by the geometric confinement provided by the templates. We have demonstrated the capability and feasibility of this approach by assembling polystyrene beads and silica colloids (> or =150 nm in diameter) into complex aggregates that include polygonal or polyhedral clusters, linear or zigzag chains, and circular rings. We have also been able to generate hybrid aggregates in the shape of HF or H2O molecules that are composed of polymer beads having different diameters, polymer beads labeled with different organic dyes, and a combination of polymeric and inorganic beads. These colloidal aggregates can serve as a useful model system to investigate the hydrodynamic and optical scattering properties of colloidal particles having nonspherical morphologies. They should also find use as the building blocks to generate hierarchically self-assembled systems that may exhibit interesting properties highly valuable to areas ranging from photonics to condensed matter physics.
Chemotherapeutics are the most effective treatment for metastatic tumours. However, the ability of cancer cells to become simultaneously resistant to different drugs--a trait known as multidrug resistance--remains a significant impediment to successful chemotherapy. Three decades of multidrug-resistance research have identified a myriad of ways in which cancer cells can elude chemotherapy, and it has become apparent that resistance exists against every effective drug, even our newest agents. Therefore, the ability to predict and circumvent drug resistance is likely to improve chemotherapy.
Oriented attachment is the key: Single crystalline ZnO nanorods with lengths up to 500 nm could be prepared in a stepwise manner from quasi-spherical nanoparticles. Only after the formation of pearl-chain-like structures (left), do the aggregated particles fuse upon heating to form nanorods (center and right).
Since the discovery of carbon nanotubes in 1991 (ref. 1), there have been significant research efforts to synthesize nanometre-scale tubular forms of various solids. The formation of tubular nanostructure generally requires a layered or anisotropic crystal structure. There are reports of nanotubes made from silica, alumina, silicon and metals that do not have a layered crystal structure; they are synthesized by using carbon nanotubes and porous membranes as templates, or by thin-film rolling. These nanotubes, however, are either amorphous, polycrystalline or exist only in ultrahigh vacuum. The growth of single-crystal semiconductor hollow nanotubes would be advantageous in potential nanoscale electronics, optoelectronics and biochemical-sensing applications. Here we report an 'epitaxial casting' approach for the synthesis of single-crystal GaN nanotubes with inner diameters of 30-200 nm and wall thicknesses of 5-50 nm. Hexagonal ZnO nanowires were used as templates for the epitaxial overgrowth of thin GaN layers in a chemical vapour deposition system. The ZnO nanowire templates were subsequently removed by thermal reduction and evaporation, resulting in ordered arrays of GaN nanotubes on the substrates. This templating process should be applicable to many other semiconductor systems.
An interfacial sol-gel synthesis of inorganic hollow microspheres in room-temperature ionic liquids is newly developed. When metal alkoxides such as titanium tetrabutoxide, Ti(OBu)4, are dissolved in anhydrous toluene and injected into 1-buthyl-3-methylimidazolium hexafluorophosphate ([C4mim]PF6) under vigorous stirring, hollow titania microspheres are formed. The present technique is widely applicable to the reactive metal alkoxides such as Zr(OBu)4, Hf(OBu)4, Nb(OBu)4, and InSn3(OR)x, giving a general route to the metal oxide microspheres. When gold nanoparicles and carboxylate-containing dyes such as fluorescein isothiocyanate (FITC) are dissolved in the toluene microdroplets, they are stably immobilized in the microsphere shells. Calcination of the titania gel microspheres gives anatase TiO2 microspheres. The present method provides the first example of inorganic hollow microspheres formed in ionic liquids, and the ability to modify microspheres with metal nanoparticles or functional organic molecules would be widely applied to the design of smart organic/inorganic hybrid materials.
Monomethoxypoly(ethylene glycol)-b-poly(DL-lactide) copolymer (PELA) microparticles loading lysozyme were prepared through a modified W/O/W double emulsion-solvent diffusion method using ethyl acetate (EA) as organic solvent. The modified process was divided into five steps: (1) primary emulsification (W1/O), (2) re-emulsification (W1/O/W2), (3) pre-solidification, (4) solidification and (5) purification. The pre-solidification step was carried out in the modified process to control the diffusion rate of EA from oil phase into outer aqueous phase, in order to prevent the wall polymer from precipitation, which usually occurred when the diffusion rate was too fast. The adequately rapid solidification of microparticle caused by controlled fast diffusion of EA and the use of amphiphilic copolymer PELA as wall material, facilitated a high protein entrapment (always above 94%) and full preservation of bioactivity of entrapped lysozyme. It was found that the volume of the outer aqueous phase in the re-emulsification step and the shear stress in the pre-solidification step had a significant effect on the diffusion rate of EA from the droplets into outer aqueous solution, and thereby on the characteristics of the resultant microparticles. With the volume or the shear stress increasing, the removal rate of EA increased, resulting in rapid solidification of the microparticles. This result led to a lower burst effect and a slower lysozyme release from the microparticles. This study suggests that the modified W/O/W double emulsion-solvent diffusion method with EA as organic solvent is a prospective technique to prepare biodegradable microparticles containing water-soluble sensitive agents.
Drug smuggling: Micelles made up of block copolymers and the anticancer drug adriamycin (ADR), which is linked to the polymer by a pH-sensitive linker, have been prepared (see picture). Treatment of cancer cells with the micelles shows that the micelles are transported into the cell by endocytosis, thus bypassing the cell-membrane transporters. In the cell, the decrease in pH value triggers the release of the ADR, which retains its cytotoxic effect. The released ADR fluoresces which allows its localization within the cells to be detected.
Nonsmall cell lung carcinomas (NSCLCs) are associated with very dismal prognoses, and adjuvant chemotherapy, including irinotecan, taxanes, platin, and vinca alkaloid derivatives, offer patients only slight clinical benefits. Part of the chemoresistance of NSCLC results from the expression in NSCLC cells of a very large set of endogenous proteins, which antagonize chemotherapy-mediated attacks on these tumor cells.
The authors set up an orthotopic model of a human NSCLC by grafting A549 cells into the lungs of nude mice. They tried treating these A549 NSCLC orthotopic xenograft-bearing nude mice on the basis of various chemotherapeutic protocols, including chronic administrations of taxol, oxaliplatin, and irinotecan. A cyclooxygenase-2 (COX-2) inhibitor (NS-398) also was assayed in combination with taxol. The immunohistochemical expression levels of COX-2, prostaglandin E synthetase (PGES), ornithine decarboxylase (ODC), the lung-related resistance protein (LRP), and glutathione-S-transferase-alpha (GST-alpha), GST-mu, and GST-pi were quantitatively determined by means of computer-assisted microscopy in control and drug-treated NSCLC orthotopic xenografts.
The orthotopic A549 xenograft model developed in 100% of the grafted mice, leading to brain metastases in approximately 61% mice and to liver metastases in approximately 40% of mice. The model was resistant to taxol and oxaliplatin and was only weakly sensitive to irinotecan. High levels of chemoresistant markers (i.e., COX-2, PGES, ODC, LRP, GST-alpha, GST-mu, and GST-pi) were observed in the nontreated A549 xenografts, although with dramatic variations in individual expression. Taxol and oxaliplatin significantly increased the levels of expression of COX-2, PGES, GST-mu, and GST-pi in a number of different experimental protocols.
The A549 orthotopic xenograft model could be used to evaluate investigational chemotherapeutic agents to identify drugs rapidly that are more active than the drugs currently in use in hospitals.
Synthetic aragonite-based porous materials were drug loaded with gentamicin sulphate, an antibiotic active on Staphylococcus aureus responsible for osteomyelitis. Drug loading was accomplished by two different ways: by integration of gentamicin in material during processing or by soaking material into gentamicin solutions. We first investigated the influence of drug loading on compressive strength of materials. Results indicate that soaked materials presented the same compressive strength than unloaded materials with the same porosity. By contrast, the integration of gentamicin during processing increased significantly the compressive strength of materials. The materials drug content before elution was a least 10 times higher when gentamicin was integrated during processing comparatively to soaked materials. The study of in vitro gentamicin release showed that for materials with gentamicin integrated during material processing, high concentrations of gentamicin were released up to 8 or 12 days, against 4 days for soaked materials. The transport coefficients calculation, for the first step of release, indicated that the rate of release was higher for materials with integrated gentamicin because of the higher gentamicin content. The porosity rate influenced the rate of release for materials positively with gentamicin integrated during processing contrary to soaked materials for which a higher porosity rate allowed a deeper penetration of gentamicin during drug loading and then a slightly slower release. Results indicate that aragonite-based material with gentamicin integrated during material processing may be used either as resorbable device for release of high concentrations of gentamicin or as biomaterial for combined therapy: bone substitution and prevention or treatment of osteomyelitis.
The development of diagnostic tests to differentiate between vaccinated animals and those infected with Mycobacterium bovis is required so that test and slaughter control strategies can continue alongside vaccination. In this work, the peptide antigen, ESAT-6, p45, derived from the N-terminal sequence of the ESAT-6 protein, was adsorbed onto a range of microparticulate and nanoparticulate substrates to enhance the in vitro immune response of blood lymphocytes previously sensitised to M. bovis. Two types of hydroxyapatite (HA) nanoparticles (both approximately 300 nm in linear dimension), carbonate hydroxyapatite nanospheres (CHA, approximately 50 nm), two sizes of polystyrene nanospheres ( approximately 500 and 40 nm), calcium carbonate microparticles (0.3-1.0 microm) and glass microspheres (1.0-3.0 microm) were incubated in a solution of the peptide in PBS. Peptide adsorption increased on the nanoparticle carriers in the order HA (2.5+/-0.12%w/w), CHA (4.9+/-0.12) polystyrene (500 nm, 6.8+/-0.15%, 40 nm, 9.2+/-0.07) and these systems exhibited fairly low levels of desorption (approximately 10-15% peptide release) over a 24-h incubation period in PBS at 37 degrees C. HA, CHA and polystyrene carriers with adsorbed peptide were subsequently tested in the BOVIGAM assay to investigate the efficiency of the immune response of blood lymphocytes in terms of interferon-gamma (IFN-gamma) production. A general elevation of IFN-gamma production resulted for particle-bound peptide relative to free peptide at high peptide concentrations (>10 microg/ml). Only HA-adsorbed peptide resulted in consistently higher immune responses at low peptide concentration (<0.1 microg/ml) compared with the free peptide, indicating that peptide antigens adsorbed to hydroxyapatite nanoparticles may be useful, in diagnostic assays, for differentiating between tuberculosis (TB)-infected and vaccinated animals.
We devised a simple method for incorporating drugs into solid calcium carbonate nanoparticles (nano-CaCO3). The size of nano-CaCO3 was controlled by mixing speed. Washing the nanoparticles released little incorporated drug but much drug that was adsorbed on the surface. In an in vitro releasing test, granulocyte colony-stimulating factor incorporated in nano-CaCO3 was chemically stable and released very slowly. Subcutaneous injection of nano-CaCO3 incorporating betamethasone phosphate (BP) resulted in a smaller initial increase in plasma concentration and a subsequent sustained release in compared with betamethasone phosphate solution. Nano-CaCO3 may be useful to deliver hydrophilic drugs and bioactive proteins.
The control of size and size distribution of microspheres is necessary for obtaining repeatable controlled release behavior. The chitosan microspheres were prepared by a membrane emulsification technique in this study. Chitosan was dissolved in 1 wt.% aqueous acetic acid containing 0.9 wt.% sodium chloride, which was used as a water phase. A mixture of liquid paraffin and petroleum ether 7:5 (v/v) containing PO-500 emulsifier was used as an oil phase. The water phase was permeated through the uniform pores of a porous glass membrane into the oil phase by the pressure of nitrogen gas to form W/O emulsion. Then GST (Glutaraldehyde Saturated Toluene) as crosslinking agent was slowly dropped into the W/O emulsion to solidify the chitosan droplets. The preparation condition for obtaining uniform-sized microspheres was optimized. The microspheres with different size were prepared by using the membranes with different pore size, and there was a linear relationship between the diameter of microspheres and pore size of the membranes when the microspheres were in the range of micron size. The smallest chitosan microspheres obtained was 0.4 mum in diameter. This is the first report for preparing the uniform-sized chitosan microspheres by membrane emulsification technique. Uniform chitosan microspheres were further used as a carrier of protein drug. Bovine serum albumin (BSA) as a model drug was loaded in the microspheres and released in vitro. The effects of pH value, diameter and crosslinking degree of microspheres, and BSA concentration on loading efficiency and release behavior were discussed.
The studies described in this paper aimed to assess the stain removal efficacy, fluoride efficacy and abrasivity to enamel and dentine of a new whitening toothpaste containing calcium carbonate and perlite, using appropriate in vitro models.
Stain removal efficacy was assessed using the pellicle cleaning ratio (PCR) method. Fluoride efficacy was assessed using remineralisation, demineralisation and fluoride-uptake methods. Abrasivity was assessed using an enamel and dentine wear method.
The results showed that the new whitening toothpaste was able to remove extrinsic tooth stain more effectively than three commercially available toothpaste formulations. The fluoride efficacy was superior to a non-fluoridated control and was not significantly different to a clinically tested fluoride-containing toothpaste. The abrasivity data showed that the calcium carbonate/perlite toothpaste is no more abrasive to enamel or dentine than two other commercially available whitening toothpastes.
The studies show that the new whitening toothpaste is effective in extrinsic stain removal, has an efficacious fluoride source and does not have an undue degree of abrasivity to enamel or dentine compared to other relevant commercially available products.
To summarise clinical support for the anti-caries efficacy of fluoride toothpastes containing sodium monofluorophosphate (SMFP) and to discuss the possible means by which the abrasive particles in calcium carbonate-based SMFP toothpastes might complement and/or enhance fluoride efficacy.
The anti-caries efficacy of fluoride has been proven beyond any reasonable doubt, and the efficacy of SMFP, when incorporated into a variety of compatible toothpaste formulations, has been established in numerous clinical trials. Calcium carbonate-based toothpastes may also influence caries by effecting an increase in plaque calcium levels; an inverse relationship between plaque calcium and caries is well-established. It has also been reported that plaque fluoride levels are dependent on plaque calcium levels. Hence elevated plaque calcium resulting from the use of calcium carbonate-based toothpastes has the potential to elevate plaque fluoride, itself linked to reduced caries experience. It has been shown that calcium carbonate particles are retained by plaque and this may also influence caries by neutralising harmful plaque acids and concurrently liberating calcium.
Fluoride delivered from calcium carbonate-based SMFP toothpastes is an effective means of reducing caries. Further, calcium carbonate may confer additional benefits through elevation of oral calcium levels and neutralisation of plaque-acids.
A general method for the synthesis of metal oxide hollow spheres has been developed by using carbonaceous polysaccharide microspheres prepared from saccharide solution as templates. Hollow spheres of a series of metal oxides (SnO2, Al2O3, Ga2O3, CoO, NiO, Mn3O4, Cr2O3, La2O3, Y2O3, Lu2O3, CeO2, TiO2, and ZrO2) have been prepared in this way. The method involves the initial absorption of metal ions from solution into the functional surface layer of carbonaceous saccharide microspheres; these are then densified and cross-linked in a subsequent calcination and oxidation procedure to form metal oxide hollow spheres. Metal salts are used as starting materials, which widens the accessible field of metal oxide hollow spheres. The carbonaceous colloids used as templates have integral and uniform surface functional layers, which makes surface modification unnecessary and ensures homogeneity of the shell. Macroporous films or cheese-like nanostructures of oxides can also be prepared by slightly modified procedures. XRD, TEM, HRTEM, and SAED have been used to characterize the structures. In a preliminary study on the gas sensitivity of SnO2 hollow spheres, considerably reduced "recovery times" were noted, exemplifying the distinct properties imparted by the hollow structure. These hollow or porous nanostructures have the potential for diverse applications, such as in gas sensitivity or catalysis, or as advanced ceramic materials.
Topoisomerase I inhibitors, like topotecan, have activity in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). 9-Nitro-camptothecin (9-NC) is a new oral topoisomerase inhibitor with a good safety profile. The aims of the current study were to evaluate the activity and safety of 9-NC in MDS and CMML.
Adults with a diagnosis of MDS (n = 12) and CMML (n = 32) received 9-NC 2 mg/m(2) orally daily 5 days a week, every 4 to 6 weeks.
Overall, 5 (11%) patients achieved complete response (CR), 7 (16%) had a partial response (PR), and 6 (14%) had hematologic improvement (HI), for an overall response rate of 41%. The response rate was similar in MDS and CMML. Severe (Grade 3-4) side effects included nausea and vomiting (7%), diarrhea (18%), other gastrointestinal toxicities (5%), and genitourinary toxicities (12%).
9-NC is active in MDS and CMML. The paucity of available therapies in CMML makes 9-NC a good candidate for further studies as a single agent, or in combination with decitabine, 5-azacitidine or cytarabine.
Nuclear DNA topoisomerase I (TOP1) is an essential human enzyme. It is the only known target of the alkaloid camptothecin, from which the potent anticancer agents irinotecan and topotecan are derived. As camptothecins bind at the interface of the TOP1-DNA complex, they represent a paradigm for interfacial inhibitors that reversibly trap macromolecular complexes. Several camptothecin and non-camptothecin derivatives are being developed to further increase anti-tumour activity and reduce side effects. The mechanisms and molecular determinants of tumour response to TOP1 inhibitors are reviewed, and rational combinations of TOP1 inhibitors with other drugs are considered based on current knowledge of repair and checkpoint pathways that are associated with TOP1-mediated DNA damage.
Drug-supported spherical microparticles with below 3 microm in diameter of calcium carbonate (CC) nanocrystals were precipitated by a complex decomposition method from Na2CO3 and CaCl2 solutions with hydrocortisone phosphate (HyC). The HyC was completely incorporated into the microparticles and was adsorbed on the surface of nanocrystals. The crystal phases of vaterite and calcite were controlled by the addition of magnesium ions. Spherical microparticles of calcite cores and petal-shaped hydroxyapatite (HAp) outer layers were fabricated by soaking calcite into the SBF, or a supersaturated solution of phosphate ions to enhance the crystal growth of HAp.
An electrodispersion reactor has been used to prepare calcium alginate (Ca-alginate) microgel beads in this study. In the electrodispersion reactor, pulsed electric fields are utilized to atomize aqueous mixtures of sodium alginate and CaCO3 nanoparticles (dispersed phase) from a nozzle into an immiscible, insulating second liquid (continuous phase) containing a soluble organic acid. This technique combines the features of the electrohydrodynamic force driven emulsion processes and externally triggered gelations in microreactors (the droplets) ultimately to yield soft gel beads. The average particle size of the Ca-alginate gels generated by this method changed from 412 +/- 90 to 10 +/- 3 microm as the applied peak voltage was increased. A diagram depicting structural information for the Ca-alginate was constructed as a function of the concentrations of sodium alginate and CaCO3 nanoparticles. From this diagram, a critical concentration of sodium alginate required for sol-gel transformation was observed. The characteristic highly porous structure of Ca-alginate particles made by this technique appears suitable for microencapsulation applications. Finally, time scale analysis was performed for the electrodispersion processes that include reactions in the microreactor droplets to provide guidelines for the future employment of this technique. This electrodispersion reactor can be used potentially in the formation of many reaction-based microencapsulation systems.
A process of sequential self-transformation used to prepare in a single step high yields of crystalline tungsten trioxide hollow microspheres with amorphous internal cores that are detached from the enclosing crystalline shell was investigated. Electroc-diffraction analysis of shell fragments from individual hollow microspheres showed polycrystalline powder patterns. The apparent porous structure of the shell wall observed by scanning electron microscopy (SEM) was confirmed by Brunauer-Emmet-Teller (BET) analysis. The time dependence of the sphere-in-shell formation mechanism was elucidated by TEM and X-ray diffraction (XRD) analysis of structures isolated from the reaction mixture maintained at 80°C for various aging times. It was observed that the tungsten trioxide hollow microspheres showed a continuous absorption band below 470 nm.
Nanotechnology has shown tremendous promise in target-specific delivery of drugs and genes in the body. Although passive and active targeted-drug delivery has addressed a number of important issues, additional properties that can be included in nanocarrier systems to enhance the bioavailability of drugs at the disease site, and especially upon cellular internalization, are very important. A nanocarrier system incorporated with stimuli-responsive property (e.g., pH, temperature, or redox potential), for instance, would be amenable to address some of the systemic and intracellular delivery barriers. In this review, we discuss the role of stimuli-responsive nanocarrier systems for drug and gene delivery. The advancement in material science has led to design of a variety of materials, which are used for development of nanocarrier systems that can respond to biological stimuli. Temperature, pH, and hypoxia are examples of "triggers" at the diseased site that could be exploited with stimuli-responsive nanocarriers. With greater understanding of the difference between normal and pathological tissues and cells and parallel developments in material design, there is a highly promising role of stimuli-responsive nanocarriers for drug and gene delivery in the future.
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