【作者】 杨黎明；

【导师】 夏义本；

【作者基本信息】 上海大学 ， 材料学， 2005， 博士

【摘要】 壳聚糖（Chitosan）是虾、蟹和昆虫壳骨架中提取物甲壳素的脱乙酰产物，是自然界中唯一的碱性多糖。它来源丰富，是一种可再生的天然高分子材料。壳聚糖具有生物相容性好、易生物降解、无毒、环境友好等特性；壳聚糖及其衍生物有着广泛的用途，特别是在生物医学领域，可用作药物载体、人工软组织材料（如人工皮）等。壳聚糖富含羟基和氨基，通过改性可以得到特定的功能高分子材料。如引入羧基后可得到特殊的聚两性电解质的性能。本文通过三种改性方法，在壳聚糖中引入羧基，成功地制备了三种具有特殊pH和温度敏感性的智能水凝胶。 采用⁶⁰Co-γ射线和电子束对壳聚糖—丙烯酸混合水溶液辐照，制得了具有pH敏感性的壳聚糖（CS）／聚丙烯酸（PAAc）互穿网络水凝胶。该水凝胶在pH＜4和pH＞6的条件下溶胀较大，而在pH4至5之间的缓冲溶液中溶胀较小，具有明显的“酸”、“碱”双重敏感特性；采用反相乳液聚合法制备了CS／PAAC磁性水凝胶微球，通过溶胀吸附法将一种广谱抗癌药物—平阳霉素包埋于该磁性水凝胶微球，测定了其体外模拟药物释放的性能。动物实验结果表明，该磁微球在外磁场的作用下，能有效地进入肿瘤细胞的“靶区”，对肿瘤细胞的主动脉具有栓塞作用，同时具有药物缓释作用，对肿瘤细胞具有明显的疗效。 采用⁶⁰Co-γ射线对羧甲基壳聚糖（CMCS）和N-异丙基丙烯酰胺（NIPAAm）混合水溶液进行辐照，制得了具有温度和pH双重敏感性的聚N-异丙基丙烯酰胺（PNIPAAm）／CMCS半互穿网络水凝胶。该水凝胶将PNIPAAm温度敏感性的低临界溶解温度（LCST）由32℃提高到人体温度37℃以上，同时也大幅度提高了水凝胶的溶胀比；用考马斯亮蓝作为药物模型，研究了该共聚物水凝胶在不同温度下的药物释放性能。 采用丙酮酸对壳聚糖进行化学改性，通过丙酮酸的羰基基与壳聚糖的氨基反应生成Schiff碱化合物，再用NaBH₄进行还原，制备了聚两性电解质丙酮酸壳聚糖（PCS），然后采用聚乙二醇双缩水甘油醚为交联剂制得具有pH敏感性的丙酮酸壳聚糖（CPCS）水凝胶。该水凝胶显示出独特的酸碱两性响应性和良好的溶胀可逆性。更多还原

【Abstract】 Chitosan is obtained by alkaline deacetylation of chitin from the shell of shrimp, crab and insects etc, is an alkaline polymer, one of the abundant and reproducible natural polymers in the world. Due to the biocompatibility, biodegradable, no toxicity and environmental friendship, chitosan and its ramifications are potentially be widely applied especially in biomedical applications such as in drug delivery system and artificial soft tissues and so on. Chitosan contains hydroxyl and ammoniac in its unit structure and a special kind of polar polymer could be obtained by the introduction of carbonyl group. Three kind techniques were used for introducing carbonyl group and three kind hydrogels with special pH sensitive were obtained in this paper.⁶⁰Co γ-ray and electron beam was applied as irradiation source and the pH sensitive chitosan （CS）/poly acrylic acid （PAAc） was obtained by irradiating the solution mixture of chitosan （CS） and acrylic acid （AAc）. The CS/PAAc hydrogel obtained in this experimental swelled in the conditions of pH<4 and pH>6, but de-swelled during the pH range of 4-5, which indicated that hydrogel is sensitive in both basic and acidic solution. The magnetic hydrogel microsphere （ferrogel） was synthesized by reversed emulsion polymerization. An anticancer drug, Bleomycin A5 Hydrochloride （BLM） is immobilized into the ferrogel by swollen adsorption and the experiments in vitro and in vivo were performed. The experiment result in vivo indicated that the ferrogel could be easily droved into the targeted area near the tumor by outside magnetic field. The function of embolism and slow release of drug were approved in vivo. An obvious effect of the BLM immobilized ferrogel was observed on the healing of explanted tumor.Carboxyl methyl chitosan （CMCS）/poly-N-isopropylacrylamide （PNIPAAm） hydrogel was prepared by irradiating the aqueous solution mixture of Carboxyl methyl chitosan （CMCS） and N-isopropylacrylamide （NIPAAm） with ⁶⁰Co γ-ray. The swelling behavior was determined in the media of deionized water, different ionic strength solutions and different pH buffer solutions at different temperature, respectively. The results indicated that the low critical solution temperature （LCST） of the CMCS/PNIPAAm hydrogel could be increased above the 37℃ with the content of CMCS. On the other hand, the swelling ratio also much increased compared the homopolymer hydrogel of PNIPAAm. The drug delivery behavior of the CMCS/PNIPAAm hydrogel was studied by using Commas bright blue as the drug更多还原