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In bone cancer treatment, local delivery of chemotherapeutic agents is preferred compared to other routes of administration. Delivery of multiple drugs using biodegradable carriers improves the treatment efficiency and overcomes drug resistance and toxicity. With this approach, we have developed multilayer biodegradable core shell nanoparticles (NP...
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The results of the synthesis of magnesium matrices with a porous structure have been presented. The cavities sizes vary from 10 microns to hundreds of microns. It has been obtained porous magnesium samples coated by spin-coating with biodegradable polycaprolactone. It has been shown that a dense layer of biodegradable polymer more than 50 μm thickn...
Citations
... Our findings are compliant with the results reported for HA-doxorubicin-chitosan/polycaprolactone-MTX nanoparticles. Under physiological pH evaluation, a cumulative MTX release of 9.9 µg/mL (22%) and~11 µg/mL (24%) was recorded after 24 h and 72 h, respectively, which determined a time-dependent and dose-dependent cytotoxicity in MG-63 osteosarcoma cells [102]. Using the same human tumor cell line, more pronounced cytotoxic effects were evidenced for PLGA nanocarriers in lower doses when compared to pure MTX in higher doses. ...
The bioactive surface modification of implantable devices paves the way towards the personalized healthcare practice by providing a versatile and tunable approach that increase the patient outcome, facilitate the medical procedure, and reduce the indirect or secondary effects. The purpose of our study was to assess the performance of composite coatings based on biopolymeric spheres of poly(lactide-co-glycolide) embedded with hydroxyapatite (HA) and methotrexate (MTX). Bio-simulated tests performed for up to one week evidenced the gradual release of the antitumor drug and the biomineralization potential of PLGA/HA-MTX sphere coatings. The composite materials proved superior biocompatibility and promoted enhanced cell adhesion and proliferation with respect to human preosteoblast and osteosarcoma cell lines when compared to pristine titanium.
... Inorganic nanoparticles, especially calcium phosphate nanoparticles, are increasingly used in the field of orthopedic diseases [29,30]. Prasad et al developed multilayer nanoparticles with a hydroxyapatite-based core and a shell consisting of chitosan and polycaprolactone to deliver chemotherapy agents for the treatment of osteosarcoma [31]. Calcium phosphate-based nanocomposites are excellent drug carriers in treating orthopedic diseases, because of their extraordinary biocompatibility, components similar to bones, and calcium supply [32,33]. ...
The limited options of anabolic drugs restricts their application potential in osteoporosis treatment, despite their theoretical superiority in therapeutic efficacy over antiresorptive drugs. As a prevailing strategy, nano-delivery systems could offer a wider choice of anabolic drugs. In this study, calcium phosphate nanocomposites incorporated with simvastatin (Sim) with periostin-targeting ability were designed and prepared for osteoporosis treatment. Carboxymethyl dextran (CMD) as an anionic and hydrophilic dextran derivative was used to stabilize CaP. In addition, periosteum-targeted peptide (SDSSD) was further grafted on CMD to achieve the bone targeting function. In a one-step coordination assembly strategy, hydrophobic anabolic agent Sim and SDSSD-CMD graft (SDSSD-CMD) were incorporated into the CaP nanoparticles forming SDSSD@CaP/Sim nanocomposites. The resulting SDSSD@CaP/Sim possesses uniform size, great short-term stability and excellent biocompatibility. Moreover, SDSSD@CaP/Sim exhibited a reduced release rate of Sim and showed slow-release behaviour. As anticipated, the nanocomposites exhibited bone bonding capacity in both cellular and animal studies. Besides, SDSSD@CaP/Sim achieved obviously enhanced osteoporosis treatment effect compared to direct injection of Sim in vivo. Therefore, our findings highlight the potential of SDSSD-incorporated and CaP-based nanocomposites as a viable strategy to enhance the therapeutic efficacy of anabolic drugs for osteoporosis treatment.
... In order to achieve the therapeutic objectives of improving treatment efficiency and overcoming drug resistance and toxicity, controlled release antitumor drugs are needed in bone tissue engineering. Some examples are the combination of methotrexate (MTX) with doxorubicin (DOX) [161], and the combination of paclitaxel (PTX) with etoposide (ETP) to treat osteosarcoma [105]. ...
Bone defects have caused immense healthcare concerns and economic burdens throughout the world. Traditional autologous allogeneic bone grafts have many drawbacks, so the emergence of bone tissue engineering brings new hope. Bone tissue engineering is an interdisciplinary biomedical engineering method that involves scaffold materials, seed cells, and “growth factors”. However, the traditional construction approach is not flexible and is unable to adapt to the specific shape of the defect, causing the cells inside the bone to be unable to receive adequate nourishment. Therefore, a simple but effective solution using the “bottom-up” method is proposed. Microspheres are structures with diameters ranging from 1 to 1000 µm that can be used as supports for cell growth, either in the form of a scaffold or in the form of a drug delivery system. Herein, we address a variety of strategies for the production of microspheres, the classification of raw materials, and drug loading, as well as analyze new strategies for the use of microspheres in bone tissue engineering. We also consider new perspectives and possible directions for future development.
... Many studies have described the versatility of this material in combination with other compounds and as drugs conjugates with implanted scaffolds or polymer-coated nanoparticles [12][13][14]. Some recent studies identified nanohydroxyapatite as the preferred material for drug carrier design [7,[15][16][17][18][19][20]. Synthetic nHAp are of great interest in biomedicine as an orthopaedic and dental implant material in the form of nanoparticles, nanocoatings, porous scaffolds, or nanocomposites [21]. ...
A new combination of Toceranib (Toc; 5-[(5Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrole-3-carboxamide) with nanohydroxyapatite (nHAp) was proposed as an antineoplastic drug delivery system. Its physicochemical properties were determined as crystallinity, grain size, morphology, zeta potential and hydrodynamic diameter as well as Toceranib release. The crystalline nanorods of nHAp were synthesised by the co-precipitation method, while the amorphous Toceranib was obtained by its conversion from the crystalline form during nHAp–Toc preparation. The surface interaction between both compounds was confirmed using Fourier-transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–Vis) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The nHAp–Toc showed a slower and prolonged release of Toceranib. The release behaviour was affected by hydrodynamic size, surface interaction and the medium used (pH). The effectiveness of the proposed platform was tested by comparing the cytotoxicity of the drug combined with nHAp against the drug itself. The compounds were tested on NI-1 mastocytoma cells using the Alamar blue colorimetric technique. The obtained results suggest that the proposed platform shows high efficiency (the calculated IC50 is 4.29 nM), while maintaining the specificity of the drug alone. Performed analyses confirmed that nanohydroxyapatite is a prospective drug carrier and, when Toceranib-loaded, may be an idea worth developing with further research into therapeutic application in the treatment of canine mast cell tumour.
... Cytotoxicity was also tested by using human osteosarcoma MG 63 cell lines. These nanoparticles can be a great potential for osteocoma treatment [96]. ...
... ). SEM images of optimized electrosprayed particles prepared by single emulsion technique (i) a-d correspond to 0.3 ml, 25-10 kV voltage, and (ii) e-h correspond to 0.5 ml, 25-10 kV voltage[96]. (A higher resolution/colour version of this figure is available in the electronic copy of the article). ...
Background
Nanotechnology is a tool being used intensely in the area of drug delivery systems in the biomedical field. Electrospraying is one of the nanotechnological methods, which is growing due to its importance in the development of nanoparticles comprising bioactive compounds. It is helpful in improving the efficacy, reducing side effects of active drug elements, and is useful in targeted drug delivery. When compared to other conventional methods like nanoprecipitation, emulsion diffusion, and double emulsification, electrospraying offers better advantages to produce micro/nanoparticles due to its simplicity, cost-effectiveness, and single-step process.
Objective
The aim of this paper is to highlight the use of electrosprayed nanoparticles for biomedical applications.
Methods
We conducted a literature review on the usage of natural and synthetic materials to produce nanoparticles, which can be used as a drug delivery system for medical purposes.
Results
We summarized a possible key role of electrosprayed nanoparticles in different therapeutic applications (tissue regeneration, cancer).
Conclusion
The modest literature production denotes that further investigation is needed to assess and validate the promising role of drug-loaded nanoparticles through the electrospraying process as noninvasive materials in the biomedical field.
... The detailed flow chart is provided in Fig. 1. Among remaining articles, 23 in vitro cytotoxicity studies with 8 apoptosis examination found on osteosarcoma cell lines which carried out on MG-63 (9 articles) (Fang et al., 2017;Huang et al., 2020;Iram et al., 2017;Kamba et al., 2013;Li et al., 2017;Prasad et al., 2020;Wei et al., 2019;Yang et al., 2018Yang et al., , 2020, SaOS-2 (7 articles) (Ahmadi et al., 2020;Gu et al., 2019;Huang et al., 2020;Iram et al., 2017;Masoudi et al., 2018;Meshkini and Oveisi, 2017;Sarda et al., 2018;Tapeinos et al., 2018), MNNG-HOS (4 articles) (Fang et al., 2017;Federman et al., 2012;Huang et al., 2020;Oh et al., 2006), hFOB1.19 (3 articles) (Fu et al., 2017;Huang et al., 2020;Steckiewicz et al., 2020), U2OS (2 articles) (Fang et al., 2017;Huang et al., 2020), K7M2 (2 articles) Nguyen et al., 2016), KHOS (Wang et al., 2016), HOS (Federman et al., 2012), 143B (Steckiewicz et al., 2020), RSaOS-2 (Meshkini and Oveisi, 2017), KHOS-240S (Federman et al., 2012), HOB (Fang et al., 2017),UMR-106 (Fu et al., 2017), Rat primary osteoblast cells (Iram et al., 2017) and patient-derived cell lines (González-Fernández et al., 2017). ...
... The maximum number of cell lines used is related to Huang X's (Huang et al., 2020) study carried out with five cell lines. Different cytotoxicity tests applied such as MTT assay (15 articles) (Ahmadi et al., 2020;Fang et al., 2017;Federman et al., 2012;Fu et al., 2017;Iram et al., 2017;Kamba et al., 2013;Li et al., 2017Li et al., , 2020Masoudi et al., 2018;Meshkini and Oveisi, 2017;Nguyen et al., 2016;Prasad et al., 2020;Sarda et al., 2018;Steckiewicz et al., 2020;Wang et al., 2016), WST-8 assay (4 articles (Tapeinos et al., 2018), Trypan Blue assay (Oh et al., 2006) and Brdu assay (Kamba et al., 2013). Apoptosis examination studies consist of FITC Annexin-V staining (3 articles) (Fu et al., 2017;Li et al., 2017;Tapeinos et al., 2018), Cell Cycle assay (3 article) (Fu et al., 2017;Meshkini and Oveisi, 2017;Oh et al., 2006), Hoechst 33342 staining (2 articles) Meshkini and Oveisi, 2017), Caspase-Glo-3/7 (2 article) (González-Fernández et al., 2017;Yang et al., 2020) and PE-Annexin V/7-amino-actinomycin D (7-AAD) (Huang et al., 2020). ...
... Apoptosis examination studies consist of FITC Annexin-V staining (3 articles) (Fu et al., 2017;Li et al., 2017;Tapeinos et al., 2018), Cell Cycle assay (3 article) (Fu et al., 2017;Meshkini and Oveisi, 2017;Oh et al., 2006), Hoechst 33342 staining (2 articles) Meshkini and Oveisi, 2017), Caspase-Glo-3/7 (2 article) (González-Fernández et al., 2017;Yang et al., 2020) and PE-Annexin V/7-amino-actinomycin D (7-AAD) (Huang et al., 2020). Based on material used for NPs synthetization, three groups appeared: a) organic nanoparticles such as micelles, liposomes and organic polymers, (47.82% studies with 11 articles) (Fang et al., 2017;Federman et al., 2012;González-Fernández et al., 2017;Gu et al., 2019;Li et al., 2017Li et al., , 2020Nguyen et al., 2016;Wang et al., 2016;Wei et al., 2019;Yang et al., 2018Yang et al., , 2020 b) inorganic nanoparticles such as metal and metal oxide NPs (47.82% studies with 11 articles) (Ahmadi et al., 2020;Fu et al., 2017;Iram et al., 2017;Kamba et al., 2013;Masoudi et al., 2018;Meshkini and Oveisi, 2017;Oh et al., 2006;Prasad et al., 2020;Sarda et al., 2018;Steckiewicz et al., 2020;Tapeinos et al., 2018) and c) carbon based NPs such as graphene (4.34% studies with 1 article) (Huang et al., 2020). Morphology report of NPs stated as spherical (69.56% studies with 16 articles) (Ahmadi et al., 2020;Fang et al., 2017;Federman et al., 2012;Fu et al., 2017;Gu et al., 2019;Iram et al., 2017;Li et al., 2017Li et al., , 2020Masoudi et al., 2018;Nguyen et al., 2016;Prasad et al., 2020;Steckiewicz et al., 2020;Tapeinos et al., 2018;Wang et al., 2016;Wei et al., 2019;Yang et al., 2020), road shape (8.69% studies with 2 articles) (Kamba et al., 2013;Meshkini and Oveisi, 2017), plate-like (8.69% studies with 2 articles) (Huang et al., 2020;Oh et al., 2006), needle-like (4.34% studies with 1 article) (Sarda et al., 2018) and disk-like (4.34% studies with 1 article) (Yang et al., 2018). ...
The safe development of nanotechnology and usage of nanoparticles (NPs) require the cellular toxicity examination of these NPs. Systematic studies are necessary to collect related data and comparison of the physicochemical features of NPs and their effects on cellular viability on model systems. In the present study, we systematically reviewed original studies, which investigated the cytotoxic effects and apoptosis of free NPs (loaded with doxorubicin (Dox)/or methotrexate (MTX)) via in vitro models. Articles were systematically collected by screening the literature published online in the following databases; PUBMED and SCOPUS and Web of Science and EMBASE. 23 in vitro cytotoxicity studies with 8 apoptosis examinations were found on osteosarcoma (OS) cell lines (mostly on MG-63). 43.47% of the synthesized NPs (10 studies) showed no cytotoxicity to OS cells. 39.13% of the synthesized NPs (9 studies) showed time and/or concentration related-cytotoxicity. Potent cytotoxic synthesized NP did not state. Significance difference between the half-maximal inhibitory concentration (IC50) of drug and drug/NP reported in all studies. Involved NPs in this systematic review for delivery of Dox/or MTX to OS cells have higher safety index and biocompatibility, although small and positively charged NPs acted more toxic in comparison to larger and negative ones, apoptosis rate like cytotoxicity index was notable in drug/NP group, to apply them in clinical works. Future studies are required to address the mechanisms involved in cytotoxicity and apoptosis with a special focus on in vivo investigations.
... When a multilayer was composed of a drug and film with favorable interactions between each another, an accurate, sustainable, and controlled release formulation for anticancer therapy was formed [37].Similarly, Prasad et al examined a biodegradable, nanoparticle multilayer composed of chitosan as the outer layer and doxorubicin or methotrexate as the inner core layer, for treating osteosarcoma [38]. When these formulations were placed in differing pH environments, it was observed that in lower pH environments, 1.5 times greater amount of the drug was released. ...
... When tested on the human osteosarcoma MG 63 cell lines to compare cytotoxicity, the cell death increased by 50% as drug concentration increased after a 24 hour-incubation period. They concluded that combination multilayer delivery with biodegradable carriers showed more effective results in the treatment of osteosarcoma [38]. ...
Finding a method for drug delivery that is safe, effective, and sustainable has always been a challenge. However, one novel approach is the utilization of polyelectrolyte multilayering as a drug release platform. This method has been incorporated in not only chronic, but also, acute disease states. In this article, acute disease states such as cancer, microbials, inflammatory, and immunosuppressants are discussed; as well as chronic disease states such as hypertensives, coagulants, and diabetes. Some successes are shown with bases made of chitosan nanofilms, a combination of chitosan and alginate, gold nanorods, magnetic hollow nanospheres, pluronic nanoparticles, liposomal vesicles, phospholipids, superparamagnetic iron oxide, gelatin, and more. Additionally, a wide range of advanced technological methods were employed to observe and analyze any changes in their morphology, physicochemical properties, and drug release rates. Some challenges faced when integrating this specific drug delivery approach varied per study and are highlighted within this review.
... Encapsulation efficacy for methotrexate was increased to 85% with CS and the in-vitro drug release confirmed the sequential release of methotrexate followed by doxorubicin. The study proved that bioresorbable multi-drug nanoparticles as apromising substitute for treating several cancers [138]. In another study, Vancomycin and gentamicin were loaded into CS-MMT (montmorillonite) composites for treating post bone implantation infections. ...
Chitosan (CS) a promising biopolymer has been explored for wide biomedical applications using different technologies. Electrospraying is one of the advancing liquid atomization-based techniquesrapidly merging in fields of biomedicine, especially in drug delivery and biomedical applications.Recent studies revealed that wide therapeutics such as antibiotics, anticancer, bioactives (enzymes, growth factors, genes, cells) were successfully loaded and delivered by CS using electrospraying.Apart from the exploration of CS bioactivity in drug delivery, we attempt to brief about the electrospraying technology, parameters regulating final product quality, types of polymers used, advantages, and limitations.The scrutiny highlights different conventional to controlled delivery systems fabricated by electrosprayed CS alone or in combination with other co-polymers.Further, the comprehensive addresses the different biomedical applications like wound healing, tissue engineering, coatings for antimicrobial, bone regeneration, as dental coatings, or surface modifications based on electrosprayed CS. In comparison to other methods, CS-based coating by electrospraying technique has helped to achieve desired properties for specific functions moving many processes to product commercialization. Exploration of patents filed and published from the past decade (2009-2020) based on the electrosprayed CS in the drug delivery are listed and the trends are reported. The review is concluded with an insightful outlook and future perspective of electrosprayed CS products for their broad applications, high coherence, and safe fabrication.
... MTX/FA-CS-NPs exhibited an excellent anti-tumor activity toward HeLa cells, possibly due to the selective internalization of multifunctional NPs compared to the free drug. Recently, Prasad et al. [122] developed the multilayer core-shell CS/polycaprolactone (PCL)-NPs for co-delivery of MTX and DOX against osteosarcoma. The developed system displayed a pH-dependent sequential release of both the drugs. ...
... -Rabbit -Significantly enhanced bioavailability Improved cytotoxicity with significantly lowered IC 50 [113] DTX TPGS-CS-NPs -MDA-MB-231 -Caco-2 cell -Enhanced invitro cellular uptake and improved permeability -Enhanced invitro anticancer activity [114] DTX Ag-NCs/CS-NPs -MDA-MB-231 cell -Rabbit -Swiss albino mice -Improved oral delivery -Significantly enhanced invitro cytotoxicity -Non-significant acute toxicity [115] DTX/DOX HSA/CS-NPs -MDA-MB-231 -HeLa cell -The strong synergistic toxic effect on tumor cells -Enhanced apoptosis [116] MTX Magnetite iron-CS-NPs -MCF-7 cell -Enhanced DNA fragmentation and caspase-3 -Enhanced anti-tumor activity [117] MTX CS/Au-NPs -A549 cell -BALB/c mice -pH-dependent drug release -Enhanced drug accumulation at the tumor site -Significantly enhanced inhibition of tumor growth with no apparent toxicity [118] MTX/PMX PEG-CS-NPs -A549 cell -LLC cell -Lewis lung carcinoma bearing C57BL/6 mice -Sustained-release behavior -Enhanced cellular uptake -Significantly enhanced blood retention -Strong anti-proliferative activity -Greater S phase arrest -Vigorous synergistic invivo anticancer efficacy [119] MTX Fucoida-Cs-NPs -A549 cell -Significantly decreased IC 50 -Improved cytotoxicity -Effectively inhibits the growth and proliferation of lung carcinoma [120] MTX FA-CS-NPs -HeLa cell -Improved cellular uptake -Significantly reduced viability -Enhanced anti-proliferative activity [121] MTX/DOX CS-PCL-NPs -OMG-63 cell -pH-dependent sequential drug release -The concentration dependent cytotoxicity [122] CUR CS-NPs -SiHa cell -CaSki cell -HeLa cell -Enhanced cellular uptake -Enhanced ATP depletion [123] CUR Fungal-CS-NPs -HCT-116 cell -A549 cell -Enhanced cellular uptake -Time-dependent decrement of cell viability -Improved autophagy and apoptosis [124] CUR CS-mesoporous silica-NPs -U87MG cell -pH-dependent sustained drug release -Significantly lowered IC 50 [125] CUR Caseinate-CS-NPs -HeLa cell -Significantly enhanced CUR stability -Enhanced cellular uptake -Enhanced cytotoxicity against cancer cells [126] CUR diglutaric acid CS-alginate-NPs -Caco-2 cell -HepG cell -MDA-MB-231 cell -Better stability of drugs against UV -Enhanced invitro cellular uptake -Significantly enhanced invitro anticancer activity [127] CUR Magnetic alginate-CS-NPs [128] (continued) cationic nature have been widely explored biomaterials for gene delivery because of inherent unlimited gene packaging abilities as well as permit extensive modifications [139] . Among various polymers of cationic nature, polyethyleneimine (PEI) is very well reported in the literature for gene delivery application because of its improved transfection efficiency as well as the high ability for complexation. ...
Cancer is among the most dreadful fatal diseases globally, and the efficacy of recent chemotherapeutic approaches is limited due to many related drawbacks. The major limitation associated with cancer chemotherapy is the poor aqueous solubility of most of the anticancer drugs, development of multidrug resistance, low bioavailability, small plasma half-life, and serious side effects to healthy tissues due to unspecific distribution of chemotherapeutic drugs. Advancement in nanoscience provides the means of specific and selective targeting of cancer cells. Chitosan, one of the naturally occurring biocompatible and mucoadhesive biopolymers that have been widely used in recent years for the effective delivery of anti-cancer drugs at the target site. Chitosan nanoparticles can encapsulate both hydrophilic and lipophilic chemotherapeutic drugs, proteins/peptides as well as different genetic materials like DNA, miRNA, siRNA, etc. in their polymeric matrix. Due to the unique polymeric matrix, these nanoparticles improve the solubility as well as the stability of encapsulated molecules in the biological system. Chitosan nanoparticles can improve the pharmacokinetic profile as well as the therapeutic efficacy of encapsulated drugs by controlling the release rates and targeted delivery process. These nanoparticles selectively deliver the encapsulated drugs to desired sites through passive or active targeting mechanisms thereby decrease the undesirable side-effects. The surface of chitosan nanoparticles can be modified with different ligands like antibodies, proteins, peptides, polysaccharides, and nucleic acids to achieve selective targeting. This review will provide a state-of-the-art perspective on recent development in chitosan-nanoparticles for smart anti-cancer therapeutic delivery.
... Emulsion electrospray is an alternative route to coaxial electrospraying for the production of core-shell nanoparticles. The applications of emulsion electrospraying have been demonstrated with protein [58] and drug encapsulation [59]. Needleless emulsion electrospinning has been shown to be a promising technique for upscaling the production of core-shell nanofibers [60]. ...
This chapter considers some of the most important recent innovations in the electrospraying technology. We initially review the possibilities of processing multiple fluids simultaneously to generate complex multicompartment architectures. Most commonly two fluids are processed and the shell fluid can be independently electrosprayed into particles, while the core fluid may or may not be sprayable. This allows particles with core/shell and Janus morphologies to be prepared and can lead to improved functional performance where systems are fully optimized. Hollow materials can additionally be fabricated. Modified coaxial electrospraying, using an electrosprayable core solution and a shell fluid which cannot be electrosprayed alone, can also be performed. This has been shown to improve the quality of monolithic particles generated (by using a blank solvent as the shell-working fluid) and can also be used to apply a thin coating to particle cores. Later in the chapter, we consider the details of particle collection, and routes to avoid aggregation are discussed. Finally, scale-up of the electrospraying process is discussed, and an overview of the routes to generate industrial quantities of materials is presented.
