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Special Issue "Chitosan-Based Nanomaterials for Biomedical Applications"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 April 2019).

Special Issue Editor

Prof. Dr. Jyh-Ping Chen
Website
Guest Editor
Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan, Taiwan
Interests: biomaterials; bionanotechnoogy; tissue engineering; drug delivery; nanomedicine; bionanocomposites
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Being the second most abundant natural polymer on Earth, chitosan possesses many unique chemical, structural and biological properties that make it attractive for numerous biomedical applications. Chitosan can be easily fabricated into different nanomaterials or nanocomposites, such as nanofibers, nanoparticles, gels, micelles and liposomes, to suit different needs. In addition, numerous approaches developed for chitosan have also overcome limitations in biomedical fields by using chitosan derivatives, composites or nanocomposites. Although numerous papers have discussed the application of chitosan nanomaterials in biomedical fields, they are found dispersed in different scientific journals. Consequently, this Special Issue aims to provide a broad coverage of recent research progress or up-to-date reviews addressing various aspects in this field. With this Special Issue, we aim to provide the readers with the opportunity to learn about different facets of biomedical research using chitosan-based nanomaterials. For the authors, this Special Issue will provide a unique opportunity to make their research results more visible to the scientific community. This Special Issue is seeking contributions from researchers to discuss all application aspects of chitosan nanomaterials in tissue engineering, regenerative medicine, drug delivery, wound healing and diagnostics. Critical reviews by experts in these fields are also welcomed.

Prof. Jyh-Ping Chen
Guest Editor

Manuscript Submission Information

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Keywords

  • Chitosan
  • Tissue Engineering
  • Regenerative Medicine
  • Drug Delivery
  • Wound Healing
  • Diagnostics
  • Nanomaterials

Published Papers (11 papers)

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Research

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Open AccessArticle
The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix
Molecules 2019, 24(15), 2713; https://doi.org/10.3390/molecules24152713 - 26 Jul 2019
Abstract
Fibrotic diseases, such as Dupuytren’s contracture (DC), involve excess scar tissue formation. The differentiation of fibroblasts into myofibroblasts is a significant mechanism in DC, as it generates tissue contraction in areas without wound openings, leading to the deposition of scar tissue, and eventually [...] Read more.
Fibrotic diseases, such as Dupuytren’s contracture (DC), involve excess scar tissue formation. The differentiation of fibroblasts into myofibroblasts is a significant mechanism in DC, as it generates tissue contraction in areas without wound openings, leading to the deposition of scar tissue, and eventually flexing one or more fingers in a restrictive fashion. Additionally, DC has a high recurrence rate. Previously, we showed that N-dihydrogalactochitosan (GC), an immunostimulant, inhibited myofibroblast differentiation in a DC fibroblast culture. Our goal of this study was to expand our previous study to include other DC and normal cell lines and other chitosan derivatives (GC and single-walled carbon nanotube-conjugated GC) to determine the specific mechanism of inhibition. Derivative-incorporated and vehicle control (water) anchored fibroblast-populated collagen matrices (aFPCM) were used to monitor compaction (anchored matrix height reduction) using microscopy and optical coherence tomography (OCT) for six days. Fibroblasts were unable to compact chitosan derivative aFPCM to the same extent as vehicle control aFPCM in repeated experiments. Similarly, chitosan derivative aFPCM contracted less than control aFPCM when released from anchorage. Proliferative myofibroblasts were identified by the presence of alpha smooth muscle actin via myofibroblast proliferative assay. In all tested conditions, a small percentage of myofibroblasts and proliferative cells were present. However, when aFPCM were treated with transforming growth factor-beta 1 (TGF-β1), all tested samples demonstrated increased myofibroblasts, proliferation, compaction, and contraction. Although compaction and contraction were reduced, there was sufficient tension present in the chitosan derivative aFPCM to allow exogenous stimulation of the myofibroblast phenotype. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessArticle
Preparation, Characterization, and Release Kinetics of Chitosan-Coated Nanoliposomes Encapsulating Curcumin in Simulated Environments
Molecules 2019, 24(10), 2023; https://doi.org/10.3390/molecules24102023 - 27 May 2019
Cited by 7
Abstract
Curcumin, a natural polyphenol, has many biological properties, such as anti-inflammatory, antioxidant, and anti-carcinogenic properties, yet, its sensitivity to light, oxygen, and heat, and its low solubility in water renders its preservation and bioavailability challenging. To increase its bioaccessibility, we fabricated nanoliposomes and [...] Read more.
Curcumin, a natural polyphenol, has many biological properties, such as anti-inflammatory, antioxidant, and anti-carcinogenic properties, yet, its sensitivity to light, oxygen, and heat, and its low solubility in water renders its preservation and bioavailability challenging. To increase its bioaccessibility, we fabricated nanoliposomes and chitosan-coated nanoliposomes encapsulating curcumin, and we evaluated the systems in terms of their physicochemical characteristics and release profiles in simulated gastrointestinal mediums. Chitosan-coating enhanced the stability of nanoliposomes and slowed the release of curcumin in the simulated gastrointestinal (GI) environment. This study demonstrates that nanoliposomes and chitosan-coated nanoliposomes are promising carriers for poorly soluble lipophilic compounds with low oral bioavailability, such as curcumin. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessArticle
Effect of Geometrical Structure, Drying, and Synthetic Method on Aminated Chitosan-Coated Magnetic Nanoparticles Utility for HSA Effective Immobilization
Molecules 2019, 24(10), 1925; https://doi.org/10.3390/molecules24101925 - 18 May 2019
Cited by 4
Abstract
Human serum albumin (HSA) is one of the most frequently immobilized proteins on the surface of carriers, including magnetic nanoparticles. This is because the drug–HSA interaction study is one of the basic pharmacokinetic parameters determined for drugs. In spite of many works describing [...] Read more.
Human serum albumin (HSA) is one of the most frequently immobilized proteins on the surface of carriers, including magnetic nanoparticles. This is because the drug–HSA interaction study is one of the basic pharmacokinetic parameters determined for drugs. In spite of many works describing the immobilization of HSA and the binding of active substances, research describing the influence of the used support on the effectiveness of immobilization is missing. There are also no reports about the effect of the support drying method on the effectiveness of protein immobilization. This paper examines the effect of both the method of functionalizing the polymer coating covering magnetic nanoparticles (MNPs), and the drying methods for the immobilization of HSA. Albumin was immobilized on three types of aminated chitosan-coated nanoparticles with a different content of amino groups long distanced from the surface Fe3O4-CS-Et(NH2)1–3. The obtained results showed that both the synthesis method and the method of drying nanoparticles have a large impact on the effectiveness of immobilization. Due to the fact that the results obtained for Fe3O4-CS-Et(NH2)2 significantly differ from those obtained for the others, the influence of the geometry of the shell structure on the ability to bind HSA was also explained by molecular dynamics. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessArticle
Synergistic Effects of Photo-Irradiation and Curcumin-Chitosan/Alginate Nanoparticles on Tumor Necrosis Factor-Alpha-Induced Psoriasis-Like Proliferation of Keratinocytes
Molecules 2019, 24(7), 1388; https://doi.org/10.3390/molecules24071388 - 09 Apr 2019
Cited by 3
Abstract
Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of the epidermal cells and is clinically presented as thick, bright red to pink plaques with a silvery scale. Photodynamic therapy (PDT) using visible light has become of increasing interest in the treatment [...] Read more.
Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of the epidermal cells and is clinically presented as thick, bright red to pink plaques with a silvery scale. Photodynamic therapy (PDT) using visible light has become of increasing interest in the treatment of inflammatory skin diseases. In this study, we demonstrate that a combination of curcumin-loaded chitosan/alginate nanoparticles (Cur-CS/Alg NPs) and blue light emitting diodes (LED) light irradiation effectively suppressed the hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced cultured human kerlatinocyte (HaCaT) cells. The Cur-CS/Alg NPs were fabricated by emulsification of curcumin in aqueous sodium alginate solution and ionotropic gelation with calcium chloride and chitosan using an optimized formulation derived from a Box-Behnken design. The fabricated Cur-CS/Alg NPs were characterized for their particle size, zeta potential, encapsulation efficiency, and loading capacity. The surrogate 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, to measure the relative number of viable cells, showed that the CS/Alg NPs were nontoxic to normal HaCaT cells, while 0.05 µg/mL and 0.1 µg/mL of free curcumin and Cur-CS/Alg NPs inhibited the hyperproliferation of HaCaT cells induced by TNF-α. However, the Cur-CS/Alg NPs demonstrated a stronger effect than the free curcumin, especially when combined with blue light irradiation (10 J/cm2) from an LED-based illumination device. Therefore, the Cur-CS/Alg NPs with blue LED light could be potentially developed into an effective PDT system for the treatment of psoriasis. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessArticle
In Vitro Enzymatic Digestibility of Glutaraldehyde-Crosslinked Chitosan Nanoparticles in Lysozyme Solution and Their Applicability in Pulmonary Drug Delivery
Molecules 2019, 24(7), 1271; https://doi.org/10.3390/molecules24071271 - 01 Apr 2019
Cited by 8
Abstract
Herein, the degradation of low molecular weight chitosan (CS), with 92% degree of deacetylation (DD), and its nanoparticles (NP) has been investigated in 0.2 mg/mL lysozyme solution at 37 °C. The CS nanoparticles were prepared using glutaraldehyde crosslinking of chitosan in a water-in-oil [...] Read more.
Herein, the degradation of low molecular weight chitosan (CS), with 92% degree of deacetylation (DD), and its nanoparticles (NP) has been investigated in 0.2 mg/mL lysozyme solution at 37 °C. The CS nanoparticles were prepared using glutaraldehyde crosslinking of chitosan in a water-in-oil emulsion system. The morphological characterization of CS particles was carried out using scanning electron microscopy (SEM) and Transmission Electron Microscopy (TEM) techniques. Using attenuated total reflectance Fourier transform infrared (ATR-FTIR) and UV-VIS spectroscopy, the structural integrity of CS and its NPs in lysozyme solution were monitored. The CS powder showed characteristic FTIR bands around 1150 cm−1 associated with the glycosidic bridges (C-O-C bonds) before and after lysozyme treatment for 10 weeks, which indicated no CS degradation. The glutaraldehyde crosslinked CS NPs showed very weak bands associated with the glycosidic bonds in lysozyme solution. Interestingly, the UV-VIS spectroscopic data showed some degradation of CS NPs in lysozyme solution. The results of this study indicate that CS with a high DD and its NPs crosslinked with glutaraldehyde were not degradable in lysozyme solution and thus unsuitable for pulmonary drug delivery. Further studies are warranted to understand the complete degradation of CS and its NPs to ensure their application in pulmonary drug delivery. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessArticle
Galactosylated Chitosan-Functionalized Mesoporous Silica Nanoparticle Loading by Calcium Leucovorin for Colon Cancer Cell-Targeted Drug Delivery
Molecules 2018, 23(12), 3082; https://doi.org/10.3390/molecules23123082 - 26 Nov 2018
Cited by 6
Abstract
Targeted drug delivery to colon cancer cells can significantly improve the efficiency of treatment. We firstly synthesized carboxyl-modified mesoporous silica nanoparticles (MSN–COOH) via two-step synthesis, and then developed calcium leucovorin (LV)-loaded carboxyl-modified mesoporous silica nanoparticles based on galactosylated chitosan (GC), which are galectin [...] Read more.
Targeted drug delivery to colon cancer cells can significantly improve the efficiency of treatment. We firstly synthesized carboxyl-modified mesoporous silica nanoparticles (MSN–COOH) via two-step synthesis, and then developed calcium leucovorin (LV)-loaded carboxyl-modified mesoporous silica nanoparticles based on galactosylated chitosan (GC), which are galectin receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), nitrogen sorption, and dynamic light scattering (DLS). Drug release properties and drug loading capacity were determined by ultraviolet spectrophotometry (UV). [email protected]–COOH/GC had a high LV loading and a drug loading of 18.07%. In vitro, its release, mainly by diffusion, was sustained release. Cell experiments showed that in SW620 cells with the galectin receptor, the [email protected]–COOH/GC metabolized into methyl tetrahydrofolic acid (MTHF) and 5-fluorouracil (5-FU)@MSN–NH2/GC metabolized into FdUMP in vivo. MTHF and 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) had combined inhibition and significantly downregulated the expression of thymidylate synthase (TS). Fluorescence microscopy and flow cytometry experiments show that MSN–COOH/GC has tumor cell targeting, which specifically recognizes and binds to the galectin receptor in tumor cells. The results show that the nano-dosing system based on GC can increase the concentrations of LV and 5-FU tumor cells and enhance their combined effect against colon cancer. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessArticle
Chitosan Nanoparticles with Encapsulated Natural and UF-Purified Annatto and Saffron for the Preparation of UV Protective Cosmetic Emulsions
Molecules 2018, 23(9), 2107; https://doi.org/10.3390/molecules23092107 - 22 Aug 2018
Cited by 7
Abstract
The aim of the present work is to evaluate the preparation of sunscreen emulsions based on chitosan (CS) nanoparticles with annatto, ultrafiltrated (UF) annatto, saffron, and ultrafiltrated saffron. Ionic gelation was used for the preparation of chitosan nanoparticles, while their morphological characteristics and [...] Read more.
The aim of the present work is to evaluate the preparation of sunscreen emulsions based on chitosan (CS) nanoparticles with annatto, ultrafiltrated (UF) annatto, saffron, and ultrafiltrated saffron. Ionic gelation was used for the preparation of chitosan nanoparticles, while their morphological characteristics and physicochemical properties were evaluated via Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), and dynamic light scattering (DLS). Results showed that the prepared nanoparticles ranged from ~150 to ~500 nm and had a spherical or irregular shape. In the case of annatto and UF annatto, due to the formation of H-bonds, the sunscreen agents were amorphously dispersed within CS nanoparticles, while in the case of saffron and UF saffron, crystalline dispersion was observed. All encapsulated materials had good thermal stability as well as color stability. In a further step, sunscreen emulsions were prepared based on the formed CS-sunscreen nanoparticles and evaluated for their stability in terms of pH and viscosity, along with their ultraviolet (UV) radiation protection ability in terms of sun protection factor (SPF). All prepared emulsions showed low cytotoxicity and good storage stability for up to 90 days, while minimum sunscreen protection was observed with SPF values varying from 2.15 to 4.85. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Review

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Open AccessReview
Application of Chitosan in Bone and Dental Engineering
Molecules 2019, 24(16), 3009; https://doi.org/10.3390/molecules24163009 - 19 Aug 2019
Cited by 10
Abstract
Chitosan is a deacetylated polysaccharide from chitin, the natural biopolymer primarily found in shells of marine crustaceans and fungi cell walls. Upon deacetylation, the protonation of free amino groups of the d-glucosamine residues of chitosan turns it into a polycation, which can [...] Read more.
Chitosan is a deacetylated polysaccharide from chitin, the natural biopolymer primarily found in shells of marine crustaceans and fungi cell walls. Upon deacetylation, the protonation of free amino groups of the d-glucosamine residues of chitosan turns it into a polycation, which can easily interact with DNA, proteins, lipids, or negatively charged synthetic polymers. This positive-charged characteristic of chitosan not only increases its solubility, biodegradability, and biocompatibility, but also directly contributes to the muco-adhesion, hemostasis, and antimicrobial properties of chitosan. Combined with its low-cost and economic nature, chitosan has been extensively studied and widely used in biopharmaceutical and biomedical applications for several decades. In this review, we summarize the current chitosan-based applications for bone and dental engineering. Combining chitosan-based scaffolds with other nature or synthetic polymers and biomaterials induces their mechanical properties and bioactivities, as well as promoting osteogenesis. Incorporating the bioactive molecules into these biocomposite scaffolds accelerates new bone regeneration and enhances neovascularization in vivo. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessReview
Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives
Molecules 2019, 24(14), 2570; https://doi.org/10.3390/molecules24142570 - 15 Jul 2019
Cited by 9
Abstract
Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of [...] Read more.
Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising in vitro and in vivo results. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessReview
Chitosan-Based (Nano)Materials for Novel Biomedical Applications
Molecules 2019, 24(10), 1960; https://doi.org/10.3390/molecules24101960 - 21 May 2019
Cited by 18
Abstract
Chitosan-based nanomaterials have attracted significant attention in the biomedical field because of their unique biodegradable, biocompatible, non-toxic, and antimicrobial nature. Multiple perspectives of the proposed antibacterial effect and mode of action of chitosan-based nanomaterials are reviewed. Chitosan is presented as an ideal biomaterial [...] Read more.
Chitosan-based nanomaterials have attracted significant attention in the biomedical field because of their unique biodegradable, biocompatible, non-toxic, and antimicrobial nature. Multiple perspectives of the proposed antibacterial effect and mode of action of chitosan-based nanomaterials are reviewed. Chitosan is presented as an ideal biomaterial for antimicrobial wound dressings that can either be fabricated alone in its native form or upgraded and incorporated with antibiotics, metallic antimicrobial particles, natural compounds and extracts in order to increase the antimicrobial effect. Since chitosan and its derivatives can enhance drug permeability across the blood-brain barrier, they can be also used as effective brain drug delivery carriers. Some of the recent chitosan formulations for brain uptake of various drugs are presented. The use of chitosan and its derivatives in other biomedical applications is also briefly discussed. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessReview
Chitosan-Based Nanomaterials for Drug Delivery
Molecules 2018, 23(10), 2661; https://doi.org/10.3390/molecules23102661 - 16 Oct 2018
Cited by 36
Abstract
This review discusses different forms of nanomaterials generated from chitosan and its derivatives for controlled drug delivery. Nanomaterials are drug carriers with multiple features, including target delivery triggered by environmental, pH, thermal responses, enhanced biocompatibility, and the ability to cross the blood-brain barrier. [...] Read more.
This review discusses different forms of nanomaterials generated from chitosan and its derivatives for controlled drug delivery. Nanomaterials are drug carriers with multiple features, including target delivery triggered by environmental, pH, thermal responses, enhanced biocompatibility, and the ability to cross the blood-brain barrier. Chitosan (CS), a natural polysaccharide largely obtained from marine crustaceans, is a promising drug delivery vector for therapeutics and diagnostics, owing to its biocompatibility, biodegradability, low toxicity, and structural variability. This review describes various approaches to obtain novel CS derivatives, including their distinct advantages, as well as different forms of nanomaterials recently developed from CS. The advanced applications of CS-based nanomaterials are presented here in terms of their specific functions. Recent studies have proven that nanotechnology combined with CS and its derivatives could potentially circumvent obstacles in the transport of drugs thereby improving the drug efficacy. CS-based nanomaterials have been shown to be highly effective in targeted drug therapy. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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