Review
Chitosan centered bionanocomposites for medical specialty and curative applications: A review

https://doi.org/10.1016/j.ijpharm.2017.06.079Get rights and content

Abstract

The polyfunctional nature of chitosan enables its application not only in polymer technology but also shows their importance in the field of nanotechnology for the fabrication of the wide spectrum of functional nanomaterials in biomedical field. Chitosan is a poly aminosaccharide with appealing structure composed of β-(1  4)-linked D-glucosamine (deacetylated unit) and N-acetyl-d-glucosamine (acetylated unit). It has various functional groups that enriches for various properties such as antibacterial, mucoadhasive, nontoxic, biodegradable, biocompatible. With the advancement of material technologies, chitosan is being chemically modified into self-assembled nanocomposites for advanced biomedical applications. This review article demonstrate the various schemes for the preparation of chitosan nanocomposites from different functional material, focusing on their application specifically in tissue engineering, drug and gene delivery, wound healing and bioimaging.

Introduction

Biomaterials are the substances that have been engineered in order to interact with the biological systems for various medical purposes including therapeutic i.e. treatment, augmentation, repair or replacement of tissue as well as diagnostic (Peppas and Langer, 1994). Presently, the functionalization of biomaterials is one of the emerging processes. Among all composites; the nanocomposites are on the forefront of research and technology development especially for therapeutic purposes. Technically, nanocomposites are comprised of biopolymers instead of synthetic and/or petroleum-derived polymers. More often, they are classified into a specific classis of materials referred as “bionanocomposites” are the nanomaterials which implicate a biopolymer of natural origin in combination with an inorganic moiety, and display different in properties like biocompatibility and biodegradability (Shchipunov, 2012, Jayakumar et al., 2010, Varma et al., 2004, Darder et al., 2007). Despite their functional properties, biocomposites were synthesized and formally designed in clinical use as they were found useful in solving a problem and frequently stated for mineralized tissues of living organisms called as bio-minerals for example; crabs and shellfish, sponges corals etc. are worth mentioning sources for the extraction of chitosan. Chitosan and its derivatives are excellent material for biomedical and pharmaceutical applications and are compatible with human body environments. The pioneer work carried by Rouget (1859) have provided the acetyl free form material known as chitosan, revolutionized the field of biopolymer chemistry and is now considered as “Polymer for the Future” (Dutta et al., 2004a). The advancement in biomaterial was initiated in the early 1990s and continues to present. However, the use of chitosan, collagen, alginate, and the PEG network and their porous formulations as inert and non-biodegradable hydrogel materials are based on both natural and synthetic biomaterials with their relative chemistries to current application. The choice of biocompatible polymer used in tissue engineering is critical. Most commonly used natural polymers and synthetic polymer such as GAG and PLGA respectively, find its use in biomedical application. Chitosan is a natural polysaccharide composed of special functionality and unique structure with various applications in biomedical and other fields such as agriculture, adsorption of metals from water, cosmetics and toiletries, fibers and textiles, food, beverages, optical and paper technology (Sugiyama et al., 2001, Upadhyaya et al., 2014, Muzzarelli and Muzzarelli, 2005, Agrawal et al., 2010, Yang et al., 2014, Lee et al., 2009a, Yoksan and Chirachanchai, 2008). The chemical modifications of chitosan have been involved in improving the thermal stability and numerous properties in the field of biopolymer chemistry (Ravi Kumar, 2000). For example, structural derivatization of chitosan by introducing the groups such as carboxymethyl or alkyl further enhances its solubility at neutral pH without affecting the cationic property (Ahmad et al., 2015). It also carries the ability of nanocomposite formation, may be used as effective materials in various areas for controlling and efficient drug release functionalities. Different constituents are used to carry the drugs to the targeted sites which are mostly liposomes in carrying genes and cancer therapy (Torchilin, 2001, Torchilin, 2005). Large work has been carried by researchers for the fabrication of chitosan-based nanocomposites for biomedical applications. Zhang et al. have synthesized HA/CS nanofiber as a functional material applied to bone repair engineering (Zhang et al., 2008). Chitosan-gelatin framework with three-dimensional channel structures provides an excellent material for the treatment of liver epidemic (Gong et al., 2014). Cross-linked hyaluronic acid, hydroxyapatite nanoparticles and chitosan nanofibers with collagen(I) which are used in cartilage tissue engineering with high mechanical response (Jan et al., 2007). Chitosan and polyethylene oxide were fabricated and act as ECM and release dual growth factor for wound healing (Chaudhari et al., 1974). VEGF was successfully conjugated to chitosan formulating a novel nanocomposite with improved solubility which finds application in wound healing (Das and Baker, 2016). Grafting of chitosan (low molecular weight) with PEI-C was used for the preparation of a multifunctional copolymer-anticancer conjugate (Yu et al., 2016).

Microbiologists and biotechnologists take the advantage of chemical modification of chitosan and planned it in various forms such as chitosan-based nanocomposites. Currently, significant interests are being developed for the formation of nanostructures with increasing complexity and functionality and their possible applications in biomedicine, optoelectronics, and tissue engineering fields (Le et al., 2015). This article is dedicated to specific aspects of bionanocomposites materials, especially in term of medical specialty and curative purposes which is one of the sections of current research activities commencing of late. It is also briefly discusses approaches for their structure, some properties, and preparation/modification, techniques and formulates the applications of chitosan nanocomposites in biomedical and pharmaceuticals.

The scope of this review is the quick data sheet, highlights the use of chitosan based bionanocomposites and their research progress that are quite important for the advancement in various fields that have provided in last decades by the researchers. It also delivers the use of nanomaterials in biomedical field either alone or in association with other functional materials.

Chitosan is a β (1–4) linked linear copolymer consists of 2-acetamido-2-deoxy-d-glucopyranose and 2-amino-2-deoxy-d-glycopyranos. Its structure is very similar to cellulose, only differing in the presence of an amine (-NH2) group in place of hydroxyl (-OH) group at the C2 position available in cellulose. It is a natural polysaccharide carrying a large number of amino (-NH2) and hydroxyl (-OH) groups (Fig. 1b) with special functionality, unique structure (Dutta et al., 2004b). It is obtained from chitin (2-acetamido-2-deoxy-d-glucopyranose) in Fig 1(a), which is obtained from the exoskeleton of crustaceans, insects and several fungi by alkaline deacetylation. De-acetylation of chitin is usually conducted under the protection of nitrogen or by adding sodium borohydride to the NaOH solution to avoid undesirable side reactions (Younes and Rinaudo, 2015). It has been used as functional material in various fields due to its several properties such as biodegradability, biocompatibility, less toxicity, antimicrobial activity. It is insoluble in aqueous and organic solvents but soluble in diluted acetic acid, lactic acid, formic acid (Rinaudo, 2006). The physicochemical properties of chitosan are affected by various factors i.e. degree of de-acetylation, molecular weight, crystallinity, degradation etc (Ghosh and Ali, 2012) and the enhancement of properties may be the presence of amino and hydroxyl groups in the molecular chain and offers other advantages such as easy processing into various forms as shown in Fig. 2 offers the opportunity for the desired functional material in various fields discussed in the down text.

Section snippets

Applications

Bionanocomposites are used in fabrication of scaffolds and implants, diagnostics and biomedical devices and drug-delivery systems. It has also used in the field of cosmetics industries with the improved results; besides these applications it has taken a forthfront in medicinal field. In principle, chitosan bionanocomposites are substituting the current materials on the basis of their versatile approach.

A peculiar property of the chitosan is its polyelectrolyte nature; thus its charging is pH

Chitosan as bionanocomposites: the future prospect

The significant attention towards the combination of chitosan with organic/inorganic nanoparticles known as chitosan bionanocomposites, obtained from various active materials with different applications in the medical field as shown in Table 1. Recent years have witnessed the advanced progress in the applications of chitosan have played an extraordinary role especially in material science, agriculture and the biomedical field (Upadhyaya et al., 2014). It is considered to have improved existing

Conclusion

In this article, we have discussed the important functions of the groups that are formed from the hybrid material based on the natural polymer and their additives, which are used extensively in the biomedical application. Bionanocomposites are cross functional material derived from the biodegradable natural, synthetic polymers and inorganic/organic additives. The different chemistry and composition of the bionanocomposites leads to medical and curative specialty. The important underlying

Acknowledgements

The author Mudasir Ahmad is highly thankful to university grants commission of India for financial support, through Basic Science Research (BSR) Fellowship.

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