Polyelectrolyte Complexes of Partially Betainated Chitosan Derivatives Soluble in Weakly Alkaline Media

The design of biologically active dosage forms based on chitosan is significantly limited by its insolubility at pH values above 6.0–6.5 and worsening of its gastrointestinal absorption capacity upon transition to neutral and alkaline environmental conditions. The partial acylation of short-chain chitosans with the use of betaine in the presence of a coupling reagent (betaination) allows one to synthesize noncytotoxic derivatives soluble in an alkaline medium and preserving a high antibacterial activity in weakly alkaline physiological media, which makes them promising for application in pharmaceutical compositions. This study addresses the formation of polyelectrolyte complexes of partially betainated short-chain chitosans with different chain length and degree of betaination with a weak polyacid in acidic and weakly alkaline media. As a polyanion, a regularly alternating copolymer of maleic acid and N-vinylpyrrolidone is used, one of the advantages of which is its ability to be involved in chemical modification with various ligands, including biologically active ones. It is shown that soluble polyelectrolyte complexes can be formed by the direct mixing of components in a weakly alkaline medium (pH 7.4). The range of solubility of the complexes ([polycation] : [polyanion]) in a weakly alkaline medium is wider than that in an acidic one. Nonstoichiometric soluble polyelectrolyte complexes are also prepared using partially betainated chitosans as lyophilizing polyelectrolytes. The structure of soluble polyelectrolyte complexes of various compositions is investigated by static and dynamic light scattering as well as electrophoretic light scattering. The data obtained suggest that, both in the acidic and weakly alkaline medium, the polyelectrolyte complexes occur as polymolecular particles with either negative or positive surface charge. The results of this study can be used for designing new biocompatible and biodegradable delivery systems for biologically active compounds and genetic material.