Figure 7
Microscopic observations of capsule/MDA-MB-231 cell interactions after 24 h of culture. (A, A′) Interaction of HA-containing capsules with MDA-MB-231 cells (nuclei stained in blue and β-tubulin in pink). (B) Interaction is inhibited by adding soluble HA to the culture medium. (C−E) Immunostaining of β-tubulin (pink) and nuclei (blue) in representative MDA-MB-231 cells after 24 h of culture (C) in contact with control capsules at HD (120 capsules/cell), (D) in contact with soluble PTX at 0.0228 μM ( 1 / 40 ), and (E) in contact with PTX-loaded capsules at MD (60 capsules/cell).
Source publication
A novel type of biocompatible hollow capsules
that combine severable favorable features as a hydrophobic drug
carrier, including host−guest complexation in the shell, the
unique biological functions of hyaluronic acid (HA), and
transport properties of the multilayer shell, was designed and
prepared. These capsules were generated by layer-by-layer (...
Contexts in source publication
Context 1
... the presence of (HA-CD/PLL) 4 /HA capsules, we noted that several capsules interacted with the MDA-MB-231 cells ( Figure 7A,A′). The OG-PTX-loaded capsules were in close contact with the cells, but no internalization of the capsules could be observed ( Figure SI 7). ...
Context 2
... the presence of (HA-CD/PLL) 4 /HA capsules, we noted that several capsules interacted with the MDA-MB-231 cells ( Figure 7A,A′). The OG-PTX-loaded capsules were in close contact with the cells, but no internalization of the capsules could be observed ( Figure SI 7). This is in line with previous experiments showing that these cancer cells are unable to internalize capsules of ∼4 μm in diameter. ...
Context 3
... is in line with previous experiments showing that these cancer cells are unable to internalize capsules of ∼4 μm in diameter. 34 Of note, when soluble HA was added to the culture medium, the interaction was fully inhibited ( Figure 7B). Thus, the interaction of the HA-containing capsules and the cancer cells appears to be specifically mediated by the CD44 receptor. ...
Context 4
... PTX is known to drastically affect cell internal structures, especially nuclear and microtubule organ- ization. 38 We thus examined by immunostaining the organ- ization of β-tubulin and the nucleus ( Figure 7C−E). On control cells (no capsules or unloaded capsules), the nuclei were intact and the microtubule network was well organized (Figures 7C and data not shown). ...
Context 5
... control cells (no capsules or unloaded capsules), the nuclei were intact and the microtubule network was well organized (Figures 7C and data not shown). When PTX was added in the solution, bundles of microtubules were visible, and the nuclei were fragmented ( Figure 7D). In the presence of PTX-loaded capsules, the fragmentation of the nuclei was particularly visible at high density, and bundles of microtubules were also visible after 1 day of culture ( Figure 7E). ...
Context 6
... PTX was added in the solution, bundles of microtubules were visible, and the nuclei were fragmented ( Figure 7D). In the presence of PTX-loaded capsules, the fragmentation of the nuclei was particularly visible at high density, and bundles of microtubules were also visible after 1 day of culture ( Figure 7E). This stabilization of the microtubules resulted in defects in cell mitosis and the presence of large, multinucleated cells. ...
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Citations
... The studies on MDA-MB-231 cells indicated that HA exhibited-controlled release in addition to constant release of PTX drug from the capsule on the targeted area that killed the breast cancer cells. Hence, HA-CD capsules showcased excellent potential in delivering hydrophobic drugs to tumor cells in a controlled manner [20]. ...
This review presented the unique characteristic of different types of cyclodextrin polymers by non-covalent host-guest interactions to synthesize an inclusion complex. Various cancers are treated with different types of modified Cyclodextrins along with the anticancer drug Paclitaxel. PTX acts as a mitotic inhibitor but due to its low dissolution and permeability in aqueous solutions, it depicts considerable challenges for drug delivery system (DDS) designs. To enhances the solubility, it is reformulated with derivatives of cyclodextrins using freeze-drying, co-solvent lyophilization methods. The present supramolecular assemblies involve cyclodextrin as a key mediator which is encapsulated with paclitaxel and their controlled release at the targeted area is highlighted using different DDS. Also, the cyclodextrins applications in cancer treatment reducing off-target effects is briefly demonstrated using various types of cancer cell lines. New nano-formulation of PTX is used to improve the antitumor activity than normal PTX DDS in lungs and breast cancer is well defined in the present review.
... The incorporation and encapsulation of small hydrophobic molecules is usually a challenge in the fabrication of LbL micro-and nanocapsules. Many works have described the conjugation of the drug or prodrug to one of the polyelectrolytes to improve its solubility, stability and transport of the therapeutic hydrophobic molecule [153][154][155][156][157][158][159][160]. Thanks to the conjugation, a better control over the release rate and an improvement in the targeting are achieved. ...
... This is very useful in pathologies like cancer, in which the control over the dosage and efficient targeting of the anticancer drug determines the success of the adopted approach [159,160]. Anticancer drugs like DOX or paclitaxel (PTX) have been successfully conjugated to a wide variety of polyelectrolytes [154,157]. Within this context, several strategies have been followed for the conjugation of the drug, including amine bond formation for the conjugation of DOX [154,158] or the use of CD to host various guest molecules into their hydrophobic cavity (Fig. 9A) [157]. For example, Jing and collaborators fabricated LbL capsules using a hyaluronic acid (HA)-CD conjugate as a building block, which was subsequently loaded with PTX. ...
... Anticancer drugs like DOX or paclitaxel (PTX) have been successfully conjugated to a wide variety of polyelectrolytes [154,157]. Within this context, several strategies have been followed for the conjugation of the drug, including amine bond formation for the conjugation of DOX [154,158] or the use of CD to host various guest molecules into their hydrophobic cavity (Fig. 9A) [157]. For example, Jing and collaborators fabricated LbL capsules using a hyaluronic acid (HA)-CD conjugate as a building block, which was subsequently loaded with PTX. ...
Polymer capsules fabricated via the layer-by-layer (LbL) approach have attracted a great deal of attention for biomedical applications thanks to their tunable architecture. Compared to alternative methods, in which the precise control over the final properties of the systems is usually limited, the intrinsic versatility of the LbL approach allows the functionalization of all the constituents of the polymeric capsules following relatively simple protocols. In fact, the final properties of the capsules can be adjusted from the inner cavity to the outer layer through the polymeric shell, resulting in therapeutic, diagnostic, or theranostic (i.e., combination of therapeutic and diagnostic) agents that can be adapted to the particular characteristics of the patient and face the challenges encountered in complex pathologies. The biomedical industry demands novel biomaterials capable of targeting several mechanisms and/or cellular pathways simultaneously while being tracked by minimally invasive techniques, thus highlighting the need to shift from monofunctional to multifunctional polymer capsules. In the present review, those strategies that permit the advanced functionalization of polymer capsules are accordingly introduced. Each of the constituents of the capsule (i.e., cavity, multilayer membrane and outer layer) is thoroughly analyzed and a final overview of the combination of all the strategies toward the fabrication of multifunctional capsules is presented. Special emphasis is given to the potential biomedical applications of these multifunctional capsules, including particular examples of the performed in vitro and in vivo validation studies. Finally, the challenges in the fabrication process and the future perspective for their safe translation into the clinic are summarized.
... The problem can be overcome by conjugation of PTX with cyclodextrin. The anti-cancer activity of the PTX-cyclodextrin conjugate has been proved in MDA-MB-231 breast cancer cells [155]. PTX-loaded cyclodextrin peptide (R8-CMβCD) enhanced the cellular uptake of PTX by reducing the efflux of PTX in tumor cells by inhibiting P-gp efflux pump. ...
Cancer is one of the most widespread deadly diseases, following cardiovascular disease, worldwide. Chemotherapy is widely used in combination with surgery, hormone and radiation therapy to treat various cancers. However, chemotherapeutic drugs can cause severe side effects due to non-specific targeting, poor bioavailability, low therapeutic indices, and high dose requirements. Several drug carriers successfully overcome these issues and deliver drugs to the desired sites, reducing the side effects. Among various drug delivery systems, polysaccharide-based carriers that target only the cancer cells have been developed to overcome the toxicity of chemotherapeutics. Polysaccharides are non-toxic, biodegradable, hydrophilic biopolymers that can be easily modified chemically to improve the bioavailability and stability for delivering therapeutics into cancer tissues. Different polysaccharides, such as chitosan, alginates, cyclodextrin, pullulan, hyaluronic acid, dextran, guar gum, pectin, and cellulose, have been used in anti-cancer drug delivery systems. This review highlights the recent progress made in polysaccharides-based drug carriers in anti-cancer therapy.
... Jing et al. [244] proposed the use of paclitaxel loaded multilayered capsules formed by alternate layers of hyaluronic acid modified with β-cyclodextrin and poly-(L-lysine) as a therapeutic tool against breast cancer cells (MDA-MB-231). These capsules remain stable under physiological conditions, undergoing a sustained release of the encapsulated drug (a complete release of the encapsulated drug was reached after 5 days). ...
Polyelectrolyte multilayered capsules (PEMUCs) obtained using the Layer-by-Layer (LbL) method have become powerful tools for different biomedical applications, which include drug delivery, theranosis or biosensing. However, the exploitation of PEMUCs in the biomedical field requires a deep understanding of the most fundamental bases underlying their assembly processes, and the control of their properties to fabricate novel materials with optimized ability for specific targeting and therapeutic capacity. This review presents an updated perspective on the multiple avenues opened for the application of PEMUCs to the biomedical field, aiming to highlight some of the most important advantages offered by the LbL method for the fabrication of platforms for their use in the detection and treatment of different diseases.
... Conjugating a functional molecule to the polyelectrolyte chain or varying the final layer of the multilayer are also options for the functionalisation of PEMCs. For instance, use of folic acid-conjugated chitosan upon DS/PRO-curcumin PEMCs [264] to improve mucoadhesive properties, and the conjugation incorporation of cyclodextrins [265,266] within multilayers and the PEMC interior. For instance, HA-conjugated β-cyclodextrin entities played host to the hydrophobic drug paclitaxel [265], as demonstrated in Figure 15. ...
... For instance, use of folic acid-conjugated chitosan upon DS/PRO-curcumin PEMCs [264] to improve mucoadhesive properties, and the conjugation incorporation of cyclodextrins [265,266] within multilayers and the PEMC interior. For instance, HA-conjugated β-cyclodextrin entities played host to the hydrophobic drug paclitaxel [265], as demonstrated in Figure 15. Polycationic cyclodextrins were also paired with ALG to act as antimicrobial agents with the capability to host guest molecules within the cyclodextrin and PEMC interior [267], demonstrating the PEMCs potential for use as a multifunctional, or even multicompartmental, drug delivery vehicle. ...
... Conjugating a functional molecule to the polyelectrolyte chain or varying the final layer of the multilayer are also options for the functionalisation of PEMCs. For instance, use of folic acidconjugated chitosan upon DS/PRO-curcumin PEMCs [264] to improve mucoadhesive properties, and the conjugation incorporation of cyclodextrins [265,266] within multilayers and the PEMC interior. For instance, HA-conjugated β-cyclodextrin entities played host to the hydrophobic drug paclitaxel [265], as demonstrated in Figure 15. ...
One of the undeniable trends in modern bioengineering and nanotechnology is the use of various biomolecules, primarily of a polymeric nature, for the design and formulation of novel functional materials for controlled and targeted drug delivery, bioimaging and theranostics, tissue engineering, and other bioapplications. Biocompatibility, biodegradability, the possibility of replicating natural cellular microenvironments, and the minimal toxicity typical of biogenic polymers are features that have secured a growing interest in them as the building blocks for biomaterials of the fourth generation. Many recent studies showed the promise of the hard-templating approach for the fabrication of nano- and microparticles utilizing biopolymers. This review covers these studies, bringing together up-to-date knowledge on biopolymer-based multilayer capsules and beads, critically assessing the progress made in this field of research, and outlining the current challenges and perspectives of these architectures. According to the classification of the templates, the review sequentially considers biopolymer structures templated on non-porous particles, porous particles, and crystal drugs. Opportunities for the functionalization of biopolymer-based capsules to tailor them toward specific bioapplications is highlighted in a separate section.
... 59 The phenomenon of the increase in complexation ability of β-CyD upon grafting has been also observed for β-CyDgrafted hyaluronic acid. 60 Authors reported paclitaxel:cyclodextrin molar ratios of 0.011, 0.00026, and 0.007 for the hyaluronic acid grafted β-CyD, β-CyD, and dimethyl-β-CyD, respectively. ...
... Indeed, paclitaxel in vitro release from the different drug delivery systems functionalized with β-CyD moieties has been reported to be 30-100% during the first 24 hr. 60,63,64 Other factors that may influence the release of paclitaxel from the gels could be different mechanical properties of the gels with different concentration of the grafted material (see the Section 3.1). The gels in which POAβCyD is substituted with POA can be considered as a good control for mechanical properties of the gels. ...
Modification of drug delivery materials with beta-cyclodextrins (β-CyD) is known to increase solubility of poorly water-soluble drugs, protect drugs from degradation and sustain release. In this study, we developed a hydrogel drug delivery system for local paclitaxel delivery using the natural polysaccharide alginate functionalized with β-CyD-moieties. Paclitaxel was chosen due to its ability to form inclusion complexes with cyclodextrins. The rheological and mechanical properties of the prepared hydrogels were characterized, as well as in vitro release of the paclitaxel and in vitro activity on PC-3 prostate cancer cells. Introduction of β-CyD-moieties into the hydrogel reduces the mechanical properties of the gels compared to nonmodified gels. However, gelation kinetics were not markedly different. Furthermore, the β-CyD-modified alginate helped to reduce undesired crystallization of the paclitaxel in the gel and facilitated paclitaxel diffusion out of the gel network. Remarkably, the β-CyD grafted alginate showed increased capacity to complex paclitaxel compared to free HPβ-CyD. Release of both paclitaxel and degradation products were measured from the gels and were shown to have cytotoxic effects on the PC-3 cells. The results indicate that functionalized alginate with β-CyDs has potential as a material for drug delivery systems.
... CD as ligands of fluorescence sensors can modulate the fluorescence properties and enhancement aqueous solubility and stability [28][29][30][31][32]. It has excellent properties, such as non-toxicity, amphiphilia, host-guest inclusion, which has been widely used in food, drug and gene delivery, template for nanoparticle formation, chiral separation, etc. [33][34][35][36][37][38]. b-CD is the most widely used CD product because of its moderate molecular hole and low production cost [29,[39][40][41][42][43]. ...
In this work, novel β-cyclodextrin-enhanced Eu3+ luminescence aggregates (CELAs) with bright red fluorescence of Eu3+ are prepared. These CELAs exhibit the quick response and highly selective sensitivity at the concentration of 50 µM Fe3+. A series of ligands (such as TTA, phen, β-cyclodextrin) sensitizes the luminescence of Eu3+ (the “antenna effect”), and metal ions–ligands interactions can differentially alter the antenna effect of ligands toward Eu3+. Addition of EDTA to chelate Fe3+ restores the fluorescence, indicating that the fluorescence quenching in the presence of Fe3+ is reversible. This research provides that CELAs integrate these merits of superior lanthanide fluorescence and the amphiphilia property of β-cyclodextrin (β-CD). It is a unique system with enhancement Eu3+ luminescence in ethanol–water system and will be applied for aqueous solution detection sensor with high selectivity and reversibility for Fe3+. On the other hand, the on-off fluorescence property of the CELAs is convenient for environmental detection system.
... Furthermore, by forming inclusion complexes, drugs are protected from being prematurely degrading and metabolizing. Also, the biocompatibility of β-CD is confirmed by a recent publication for medical application [12][13][14][15][16][17][18]. β-CD has been used to enhance apparent solubility of poorly water-soluble drugs in synthetic polymers such as poly(2hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)), polyethylene glycol (PEG) [11,[19][20][21][22][23][24][25]. ...
In this study, 6-(6-aminohexyl) amino-6-deoxy-β-cyclodextrin-gellan gum complex hydrogel (HCD-GG) was developed to enhance the affinity of anti-inflammatory drug dexamethasone (Dx) and to improve chondrogenesis and decrease the inflammatory response. The modified chemical structure was confirmed by NMR and FTIR. Mechanical and physicochemical properties were characterized by performing viscosity study, compression test, injection force test, swelling kinetic, weight loss, and morphological study. The release profile of the drug-loaded hydrogels was analyzed to confirm the affinity of the hydrophobic drugs and the matrix and characterize cumulative release. In vitro test was carried out with MTT assay, live/dead staining, glycosaminoglycan (GAGs) content, double-stranded DNA (dsDNA) content, morphological analysis, histology, and gene expression. In vivo experiment was conducted by implanting the samples under a subcutaneous area of SPD rat and cartilage defected rabbit model. The results displayed successfully synthesized HCD-GG. The gelation temperature of the modified hydrogels was decreased while the mechanical property was improved when the drug was loaded in the modified hydrogel. Swelling and degradation kinetics resulted in a higher level compared to the pristine GG but was a sufficient level to support drugs and cells. The affinity and release rate of the drug was higher in the HCD-GG group which shows an improved drug delivery system of the GG-based material. The microenvironment provided a suitable environment for cells to grow. Also, chondrogenesis was affected by the existence of Dx and microenvironment, resulting in higher expression levels of cartilage-related genes while the expression of the inflammation mediators decreased when the Dx was loaded. In vivo study showed an improved anti-inflammatory response in the drug-loaded hydrogel. Furthermore, the cartilage defected rabbit model showed an enhanced regenerative effect when the Dx@HCD-GG was implanted. These results suggest that HCD-GG and Dx@HCD-GG have the potential for cartilage regeneration along with multiple applications in tissue engineering and regenerative medicine.
... The hydrophobic anticancer drug, paclitaxel, was pre-complexed with the CD-modified HA prior to the LbL coating and CaCO 3 dissolution. Hence, after PEMC formation, the paclitaxel remained within the capsule shell [84]. Polymeric CDs may also be pre-loaded into the CaCO 3 crystal matrix via co-synthesis [85][86][87] with pre-complexed drug or as empty CDs for drug post-loading. ...
Polyelectrolyte multilayer capsules (PEMCs) templated onto biocompatible and easily degradable vaterite CaCO3 crystals via the layer-by-layer (LbL) polymer deposition process have served as multifunctional and tailor-made vehicles for advanced drug delivery. Since the last two decades, the PEMCs were utilized for effective encapsulation and controlled release of bioactive macromolecules (proteins, nucleic acids, etc.). However, their capacity to host low-molecular-weight (LMW) drugs (<1–2 kDa) has been demonstrated rather recently due to a limited retention ability of multilayers to small molecules. The safe and controlled delivery of LMW drugs plays a vital role for the treatment of cancers and other diseases, and, due to their tunable and inherent properties, PEMCs have shown to be good candidates for smart drug delivery. Herein, we summarize recent progress on the encapsulation of LMW drugs into PEMCs templated onto vaterite CaCO3 crystals. The drug loading and release mechanisms, advantages and limitations of the PEMCs as LMW drug carriers, as well as bio-applications of drug-laden capsules are discussed based upon the recent literature findings.
... This study indicated that films constructed from cyclodextrin could be administered at suitable location and improve drug delivery efficacy [161,162]. Other forms of cyclodextrin that include combination of cyclodextrin with hyaluronic acid and paclitaxel have been examined by other researchers [163,164]. These formulations allow slow release of paclitaxel and more stability of cyclodextrin [163]. ...
... Other forms of cyclodextrin that include combination of cyclodextrin with hyaluronic acid and paclitaxel have been examined by other researchers [163,164]. These formulations allow slow release of paclitaxel and more stability of cyclodextrin [163]. Recent study in the field of using nanoparticles for oral cancer treatment is listed in ...
Nanoparticles (NPs) have a great potential to be ideal carriers for delivering therapeutics to diseased sites with minimal collateral damage to normal tissues. In nanoparticulate systems, drugs are dissolved, entrapped, encapsulated, or attached to a nanoparticle matrix. Nanoparticles have controlled release rate and stability in sites of diseases. In this chapter, nanoparticulate systems for dental drug delivery, about three main oral complications of the oral cavity including dental caries, periodontal disease, and oral cancer were discussed. The role of liposomes, polymeric micelles, polymeric nanoparticles, carbon-based nanoparticles, nanohydroxyapatite, iron oxide, zirconia, silica, and silver nanoparticles was reviewed in dental caries as a most common infectious disease in human being. In the next section, using liposomes and nanofibers for periodontal treatment was studied. Furthermore, nanoparticles including liposomes, gold nanoparticles, hydrogels, liquid crystals (LC), and cyclodextrin in diagnosis, prevention, and the treatment of the oral cavity were studied. Photosensitizer nanoparticles as an oral anticancer delivery system in photodynamic treatment were reviewed.
