Multiple Roles of Chitosan in Mucosal Drug Delivery: An Updated Review

Abstract

Chitosan (CS) is a linear polysaccharide obtained by the deacetylation of chitin, which, after cellulose, is the second biopolymer most abundant in nature, being the primary component of the exoskeleton of crustaceans and insects. Since joining the pharmaceutical field, in the early 1990s, CS attracted great interest, which has constantly increased over the years, due to its several beneficial and favorable features, including large availability, biocompatibility, biodegradability, non-toxicity, simplicity of chemical modifications, mucoadhesion and permeation enhancer power, joined to its capability of forming films, hydrogels and micro- and nanoparticles. Moreover, its cationic character, which renders it unique among biodegradable polymers, is responsible for the ability of CS to strongly interact with different types of molecules and for its intrinsic antimicrobial, anti-inflammatory and hemostatic activities. However, its pH-dependent solubility and susceptibility to ions presence may represent serious drawbacks and require suitable strategies to be overcome. Presently, CS and its derivatives are widely investigated for a great variety of pharmaceutical applications, particularly in drug delivery. Among the alternative routes to overcome the problems related to the classic oral drug administration, the mucosal route is becoming the favorite non-invasive delivery pathway. This review aims to provide an updated overview of the applications of CS and its derivatives in novel formulations intended for different methods of mucosal drug delivery.

Keywords: buccal delivery; chitosan; nasal delivery; ocular delivery; oral delivery; rectal delivery; vaginal delivery.

Figure 1

Representative structure of partially N-acetylated chitosan.

Figure 2

Representative schematic structure of N, N, N-trimethyl chitosan.

Figure 3

Representative schematic structures of some examples of thiolated chitosan (CS) derivatives.

Figure 4

Chitosan-based polyelectrolyte complexes (PECs).

Figure 5

Representative structure of sulfhydryl-linked chitosan-mercaptonicotinic acid.

Figure 6

Representative structures of different types of carboxymethylated chitosan (CS): (A) O-carboxymethyl-CS; (B) N, O-carboxymethyl-CS; (C) N-carboxymethyl-CS.