Cysteine Conjugation: An Approach to Obtain Polymers with Enhanced Muco- and Tissue Adhesion

Abstract

The modification of polymers towards increasing their biocompatibility gathers the attention of scientists worldwide. Several strategies are used in this field, among which chemical post-polymerization modification has recently been the most explored. Particular attention revolves around polymer-L-cysteine (Cys) conjugates. Cys, a natural amino acid, contains reactive thiol, amine, and carboxyl moieties, allowing hydrogen bond formation and improved tissue adhesion when conjugated to polymers. Conjugation of Cys and its derivatives to polymers has been examined mostly for hyaluronic acid, chitosan, alginate, polyesters, polyurethanes, poly(ethylene glycol), poly(acrylic acid), polycarbophil, and carboxymethyl cellulose. It was shown that the conjugation of Cys and its derivatives to polymers significantly increased their tissue adhesion, particularly mucoadhesion, stability at physiological pH, drug encapsulation efficiency, drug release, and drug permeation. Conjugates were also non-toxic toward various cell lines. These properties make Cys conjugation a promising strategy for advancing polymer applications in drug delivery systems and tissue engineering. This review aims to provide an overview of these features and to present the conjugation of Cys and its derivatives as a modern and promising approach for enhancing polymer tissue adhesion and its application in the medical field.

Keywords: L-cysteine; amino acid conjugation; mucoadhesion; polymer modification; polymer-L-cysteine conjugates; tissue adhesion.

Figure 1

Graphical representation of polymer–amino acid conjugates.

Figure 2

(a) The relation between the number of publications regarding modifying polymers with L-cysteine or its derivatives and the publication year. The graph includes the division into natural and synthetic polymers. (b) The application of L-cysteine–polymer conjugation in the medical field.

Figure 3

Chemical structure of L-cysteine and its derivatives used for polymer modification: (a) L-cysteine, (b) N-acetyl-L-cysteine, (c) L-cysteine methyl and ethyl esters, (d) L-cystine, and (e) L-cystine diethyl ester.

Figure 4

Graphical representation of L-cysteine role in tissue adhesion on the example of mucoadhesion.

Figure 5

Strategies for conjugating L-cysteine and its derivatives to polymers: (a) grafting to (post-polymerization) and (b) grafting from.