Functionalized and graft copolymers of chitosan and its pharmaceutical applications

ABSTRACT

Introduction: Chitosan is the second most abundant natural polysaccharide. It belongs a family of polycationic polymers comprised of repetitive units of glucosamine and N-acetylglucosamine. Its biodegradability, nontoxicity, non-immunogenicity and biocompatibility along with properties like mucoadhesion, fungistatic and bacteriogenic have made chitosan an appreciated polymer with numerous applications in the pharmaceutical, comestics and food industry. However, the limited solubility of chitosan at alkaline and neutral pH limits its widespread commercial use. This can be circumvented by fabrication of chitosan by graft copolymerization with acyl, alkyl, monomeric and polymeric moieties.

Areas covered: Modifications like quarterization, thiolation, acylation and grafting result in copolymers with higher mucoadhesion strength, increased hydrophobic interactions (advantageous in hydrophobic drug entrapment), and increased solubility in alkaline pH, the ability for adsorption of metal ions, protein and peptide delivery and nutrient delivery. Insights on methods of polymerization, including atomic transfer radical polymerization and click chemistry are discussed. Applications of such modified chitosan copolymers in medical and surgical, and drug delivery, including nasal, oral and buccal delivery have also been covered.

Expert opinion: Despite a number of successful investigations, commercialization of chitosan copolymers still remains a challenge. Further advancements in polymerization techniques may address the unmet needs of the healthcare industry.

KEYWORDS:

• Chitosan
• copolymers
• graft polymers

Article highlights

• The limited commercial applications of chitosan is mainly due to its lack of solubility in aqueous alkaline media. Several modifications like quaternization, acylation, thiolation and grafting with monomeric or polymeric derivatives can yield copolymers with superior solubility over a wide range of pH, thermoresponsive, mucodhesive, pH-responsive and highly porous hydrogels.

• Functionalization with methyl, succinyl and PEG yields derivatives with solubility even in alkaline pH, while copolymerization with poly(acrylic acid), poly(vinyl alcohol), N-acyl moieties yields copolymers with higher water absorption capacities, decreased permeability to methanol and biomedical applications.

• ATRP- a copolymerisation method, can be controlled by control over the amount of catalyst and the reaction medium, while Click chemistry method obtains copolymers with desired topological characteristics with minimum use of organic solvents.

• Chitosan copolymers have shown their applications in wound dressing and tissue regeneration, drug delivery like; oral, buccal, sublingual and nasal routes because of mucoadhesion. Delivery of poorly water soluble drugs including anti-cancer agents, achieve target specificity, increase in the stability of highly reactive nanocarriers by coating them has also been explored successfully by various research groups.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.