Mucoadhesive Marine Polysaccharides

Abstract

Mucoadhesive polymers are of growing interest in the field of drug delivery due to their ability to interact with the body's mucosa and increase the effectiveness of the drug. Excellent mucoadhesive performance is typically observed for polymers possessing charged groups or non-ionic functional groups capable of forming hydrogen bonds and electrostatic interactions with mucosal surfaces. Among mucoadhesive polymers, marine carbohydrate biopolymers have been attracting attention due to their biocompatibility and biodegradability, sample functional groups, strong water absorption and favorable physiochemical properties. Despite the large number of works devoted to mucoadhesive polymers, there are very few systematic studies on the influence of structural features of marine polysaccharides on mucoadhesive interactions. The purpose of this review is to characterize the mucoadhesive properties of marine carbohydrates with a focus on chitosan, carrageenan, alginate and their use in designing drug delivery systems. A wide variety of methods which have been used to characterize mucoadhesive properties of marine polysaccharides are presented in this review. Mucoadhesive drug delivery systems based on such polysaccharides are characterized by simplicity and ease of use in the form of tablets, gels and films through oral, buccal, transbuccal and local routes of administration.

Keywords: alginate; carrageenan; chitosan; methods of mucoadhesive; mucoadhesive; mucoadhesive interactions.

Figure 1

Mucoadhesive dosage forms based on marine polysaccharides and methods for their delivery: (a) different forms of mucoadhesive drugs; (b) delivery routes for mucoadhesive drugs.

Figure 2

Influence of the chitosan DA on the interaction with mucin. Green and yellow dots indicate the chitosan molecule (green dots, glucosamine units; yellow dots, N-acetyl-D-glucosamine); the red line indicates the mucin molecule; η_rel—relative viscosity; ƒ _{rel min}—the point at which low-MW chitosan-containing systems show their maximum in viscosity reduction. Reprinted (adapted) with permission from [21], copyright © 2022 American Chemical Society.

Figure 3

Influence of the chitosan concentration on the interaction with mucin. Aggregation/de-aggregation of mucin particles in the presence of a cationic polymer: (a) mucin dispersion in the absence of a polymer; (b) mucin dispersion in the presence of a small portion of a polymer; (c) mucin dispersion in the presence of excess polymer. Reprinted (adapted) with permission from [22], copyright © 2022 American Chemical Society.

Figure 4

Model for the interaction between alginate and the double-globular comb structure of mucin as a function of alginate MW and chain flexibility. (a) Low-MW and stiff polyanions to interact with globular regions without influencing the preferred conformation of mucin, thus having a negligible impact on bulk properties such as size and viscosity; (b) high-Mw polyanions are more flexible and to bridge distant sites, thus influencing the conformation of mucin and favoring a reduction in the overall hydrodynamic volume. Reprinted (adapted) with permission from [56], copyright © 2022 American Chemical Society.

Figure 5

Chemical structures of the repeating disaccharide units: (a) κ-CRG; (b) ι-CRG; (c) β-CRG; (d) λ-CRG.

Figure 6

Model for the interaction between CRGs and mucin the as a function of role bonding forces in the interaction: (a) in deionized water, CRGs interact with mucin to form agglomerates. Urea as hydrogen bond breaking agents causes disaggregation of these aggregates. (b) The presence of 0.15 M NaCl suppresses mucin–polysaccharide interactions, although minor interactions of CRG and mucin were maintained under these conditions. The interaction between CRG and mucin in the presence of various additives confirms that hydrogen bonds and electrostatic interactions are involved. Scheme of mucin adapted with permission from [56], copyright © 2022 American Chemical Society.