Abstract

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.

中文翻译：

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在弱碱性介质中可溶的部分甜菜碱化壳聚糖衍生物的聚电解质复合物

摘要

基于壳聚糖的生物活性剂型的设计受到其在pH值高于6.0-6.5时的不溶性以及过渡到中性和碱性环境条件下胃肠道吸收能力的恶化的极大限制。在偶联剂的存在下，使用甜菜碱对短链壳聚糖进行部分酰化（甜菜碱化），可以合成可溶于碱性介质的非细胞毒性衍生物，并在弱碱性生理介质中保持较高的抗菌活性，这使它们有希望用于药物组合物中。这项研究解决了在酸性和弱碱性介质中，部分链化的短链壳聚糖的聚电解质复合物的形成，该短链壳聚糖具有不同的链长和甜菜碱化程度，且具有不同的链化度。ñ使用了乙烯基吡咯烷酮，其优点之一是能够参与各种配体的化学修饰，包括生物活性配体。结果表明，可通过在弱碱性介质（pH 7.4）中直接混合组分来形成可溶性聚电解质复合物。络合物（[聚阳离子]：[聚阴离子]）在弱碱性介质中的溶解度范围比在酸性介质中的溶解度范围宽。非化学计量的可溶性聚电解质复合物也可以使用部分甜化的壳聚糖作为冻干的聚电解质来制备。通过静态和动态光散射以及电泳光散射研究了各种组成的可溶性聚电解质复合物的结构。获得的数据表明，在酸性和弱碱性介质中，聚电解质复合物以带负电荷或正电荷的多分子颗粒形式存在。这项研究的结果可用于设计新的生物活性化合物和遗传物质的生物相容性和可生物降解的传递系统。