Drug Delivery Systems using Self-aggregated Chitosan Derivatives

目的是将具有细胞吸引作用的壳聚糖衍生物应用于给药系统。研究结果表明：1)水热反应有利于壳聚糖和其他缩醛的分解。通过这种处理，可以很容易地得到低分子量的壳聚糖。2)合成了具有疏水性、酚醛和羧基的新型壳聚糖衍生物。壳聚糖与醛的还原性烷基化反应及壳聚糖的氧化反应。疏水性壳聚糖衍生物有利于自聚集作用和乳液的形成。氧化壳聚糖衍生物具有独特的生物学效应。3)壳聚糖及其疏水壳聚糖衍生物作为表面活性剂，稳定油水乳状液。在这种情况下，乳液中的有机相应该被壳聚糖衍生物包裹。将疏水药物在有机溶剂中与壳聚糖在醋酸水溶液中剧烈搅拌形成乳液，并在壳聚糖中加入碱性溶液使乳液固化。将含有机相的壳聚糖在酸性溶液中再溶出，将药物包封在壳聚糖中释放。4)生物降解性是药物在系统中释放的关键步骤。制备了壳聚糖衍生物和其他可生物降解聚合物共混材料。壳聚糖共混材料提高了壳聚糖的化学性能，保持了壳聚糖的生物降解性。

Our object is application of chitosan derivatives possessed cell attracting effects to drug delivery systems. In this study, we obtained following results :1)Hydrothermal reaction is useful for decomposition of chitosan and the other acetals. Using this treatment, we can obtain chitosan with low molecular weight easily.2)New chitosan derivatives with hydrophobic, phenolic and carboxyl groups were synthesized. w by reductive alkylation reaction of chitosan with aldehyds and oxidization of chitosan. The hyrophobized chitosan derivatives is advantageous for self-aggregation effect and emulsion formation. The oxidized chitosan derivatives show a unique biological effect.3)Chitosan and hydrophobized chitosan derivatives act as a surfactant and stabilize O/W emulsion. In this situation, the organic phase in the emulsion should be encapsulated by the chitosan derivatives. The emulsion was formed by vigorous stirring of a hydrophobic drug in an organic solvent and chitosan in aqueous acetic acid and the chitosan containing the emulsion was solidified by addition of alkaline. Encapsulated drug into chitosan was released by re-dissolution of yielded chitosan containing the organic phase in acidic solution.4)Biodegradability is key-step for drug releasing in the system. Blend materials with chitosan derivatives and other biodegradable polymers were prepared. The blend materials composed chitosan enhanced chemical properties and kept biodegradability of chitosan.