Drug Delivery Systems using Self-aggregated Chitosan Derivatives

本论文的目的是将具有细胞诱导性的壳聚糖衍生物应用于药物释放系统。在本研究中，我们得到了以下结果：1)水热反应有利于壳聚糖等缩醛的分解。2)合成了具有疏水、酚基和羧基的新型壳聚糖衍生物。W是通过壳聚糖与醛的还原烷基化反应和壳聚糖的氧化得到的。疏水处理的壳聚糖衍生物具有良好的自聚集效应和乳状液形成能力。氧化壳聚糖衍生物具有独特的生物效应。3)壳聚糖和疏水壳聚糖衍生物作为表面活性剂起到稳定O/W乳状液的作用。在这种情况下，乳液中的有机相应该被壳聚糖衍生物包覆。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状液，并在碱性条件下使含有该乳状液的壳聚糖固化。将得到的含有有机相的壳聚糖在酸性溶液中重新溶解，将药物释放到壳聚糖中。4)生物降解性是药物在该体系中释放的关键步骤。制备了壳聚糖衍生物与其他可生物降解聚合物的共混材料。壳聚糖共混材料既提高了壳聚糖的化学性能，又保持了其生物降解性。

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.