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Chitosan-Based Nanomaterials for Biomedical Applications

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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) | Viewed by 90175

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Prof. Dr. Jyh-Ping Chen

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Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 33302, Taiwan
Interests: drug delivery; tissue engineering; nanobiotechnology
Special Issues, Collections and Topics in MDPI journals

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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

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Keywords

Chitosan
Tissue Engineering
Regenerative Medicine
Drug Delivery
Wound Healing
Diagnostics
Nanomaterials

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Published Papers (11 papers)

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Research

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14 pages, 7652 KiB

Open AccessArticle

The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix

by K. Tu Doan, Pratiksha Kshetri, Natthapume Attamakulsri, Derek R. Newsome, Feifan Zhou, Cynthia K. Murray, Wei R. Chen, Gang Xu and Melville B. Vaughan

Molecules 2019, 24(15), 2713; https://doi.org/10.3390/molecules24152713 - 26 Jul 2019

Cited by 3 | Viewed by 3557

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 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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14 pages, 2336 KiB

Open AccessArticle

Preparation, Characterization, and Release Kinetics of Chitosan-Coated Nanoliposomes Encapsulating Curcumin in Simulated Environments

by Mahmoud Hasan, Kamil Elkhoury, Cyril J. F. Kahn, Elmira Arab-Tehrany and Michel Linder

Molecules 2019, 24(10), 2023; https://doi.org/10.3390/molecules24102023 - 27 May 2019

Cited by 95 | Viewed by 7094

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 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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18 pages, 2822 KiB

Open AccessArticle

Effect of Geometrical Structure, Drying, and Synthetic Method on Aminated Chitosan-Coated Magnetic Nanoparticles Utility for HSA Effective Immobilization

by Marta Ziegler-Borowska, Kinga Mylkie, Mariana Kozlowska, Pawel Nowak, Dorota Chelminiak-Dudkiewicz, Anna Kozakiewicz, Anna Ilnicka and Anna Kaczmarek-Kedziera

Molecules 2019, 24(10), 1925; https://doi.org/10.3390/molecules24101925 - 18 May 2019

Cited by 12 | Viewed by 4351

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 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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14 pages, 2567 KiB

Open AccessArticle

Synergistic Effects of Photo-Irradiation and Curcumin-Chitosan/Alginate Nanoparticles on Tumor Necrosis Factor-Alpha-Induced Psoriasis-Like Proliferation of Keratinocytes

by Clinton Gomez, Chawanphat Muangnoi, Feaungthit Niyamissara Sorasitthiyanukarn, Jongkonnee Wongpiyabovorn, Pornchai Rojsitthisak and Pranee Rojsitthisak

Molecules 2019, 24(7), 1388; https://doi.org/10.3390/molecules24071388 - 9 Apr 2019

Cited by 32 | Viewed by 5421

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 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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17 pages, 57240 KiB

Open AccessArticle

In Vitro Enzymatic Digestibility of Glutaraldehyde-Crosslinked Chitosan Nanoparticles in Lysozyme Solution and Their Applicability in Pulmonary Drug Delivery

by Nazrul Islam, Hui Wang, Faheem Maqbool and Vito Ferro

Molecules 2019, 24(7), 1271; https://doi.org/10.3390/molecules24071271 - 1 Apr 2019

Cited by 61 | Viewed by 7240

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 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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18 pages, 10449 KiB

Open AccessArticle

Galactosylated Chitosan-Functionalized Mesoporous Silica Nanoparticle Loading by Calcium Leucovorin for Colon Cancer Cell-Targeted Drug Delivery

by Wei Liu, Fan Wang, Yongchao Zhu, Xue Li, Xiaojing Liu, Jingjing Pang and Weisan Pan

Molecules 2018, 23(12), 3082; https://doi.org/10.3390/molecules23123082 - 26 Nov 2018

Cited by 25 | Viewed by 5598

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 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). LV@MSN–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 LV@MSN–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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19 pages, 5136 KiB

Open AccessArticle

Chitosan Nanoparticles with Encapsulated Natural and UF-Purified Annatto and Saffron for the Preparation of UV Protective Cosmetic Emulsions

by Sonia Ntohogian, Viktoria Gavriliadou, Evi Christodoulou, Stavroula Nanaki, Smaro Lykidou, Panagiotis Naidis, Lily Mischopoulou, Panagiotis Barmpalexis, Nikolaos Nikolaidis and Dimitrios N. Bikiaris

Molecules 2018, 23(9), 2107; https://doi.org/10.3390/molecules23092107 - 22 Aug 2018

Cited by 46 | Viewed by 6830

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 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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17 pages, 441 KiB

Open AccessReview

Application of Chitosan in Bone and Dental Engineering

by Alicia Aguilar, Naimah Zein, Ezeddine Harmouch, Brahim Hafdi, Fabien Bornert, Damien Offner, François Clauss, Florence Fioretti, Olivier Huck, Nadia Benkirane-Jessel and Guoqiang Hua

Molecules 2019, 24(16), 3009; https://doi.org/10.3390/molecules24163009 - 19 Aug 2019

Cited by 197 | Viewed by 10558

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 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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34 pages, 7461 KiB

Open AccessReview

Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

by Inés Serrano-Sevilla, Álvaro Artiga, Scott G. Mitchell, Laura De Matteis and Jesús M. de la Fuente

Molecules 2019, 24(14), 2570; https://doi.org/10.3390/molecules24142570 - 15 Jul 2019

Cited by 108 | Viewed by 9761

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 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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23 pages, 712 KiB

Open AccessReview

Chitosan-Based (Nano)Materials for Novel Biomedical Applications

by Gregor Kravanja, Mateja Primožič, Željko Knez and Maja Leitgeb

Molecules 2019, 24(10), 1960; https://doi.org/10.3390/molecules24101960 - 21 May 2019

Cited by 260 | Viewed by 14176

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 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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26 pages, 3145 KiB

Open AccessReview

Chitosan-Based Nanomaterials for Drug Delivery

by Jianghua Li, Chao Cai, Jiarui Li, Jun Li, Jia Li, Tiantian Sun, Lihao Wang, Haotian Wu and Guangli Yu

Molecules 2018, 23(10), 2661; https://doi.org/10.3390/molecules23102661 - 16 Oct 2018

Cited by 342 | Viewed by 14101

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. 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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