释药用壳聚糖温敏凝胶体内外形态与溶蚀降解研究  

in vitro and in vivo Morphology and Degradation of Chitosan Based Thermosensitive Hydrogel as Drug Release Matrix

作　　者：赵江[1] 蒋国强[1] 孙佳丽[1] 张阔[2] 丁富新[1] 

机构地区：[1]清华大学化学工程系,北京100084 [2]北京大学医学部实验动物中心,北京100083

出　　处：《高校化学工程学报》2010年第3期456-461,共6页Journal of Chemical Engineering of Chinese Universities

基　　金：国家自然科学基金(20806043);化学工程联合国家重点实验室开放课题(SKL-Che-08A03)

摘　　要：壳聚糖(CTS)/甘油磷酸钠(GP)反向温敏水凝胶,可用作药物注射埋植的控释材料。今对比研究了CTS/GP凝胶体外(PBS)和体内(SD大鼠皮下)的存在状态和溶蚀降解特征。凝胶在SD大鼠皮下被疏松纤维囊壁包裹,对周边组织未产生毒性,生物相容性良好。受体内渗透压、pH值、生理反应等影响,凝胶的体内外存在状态和溶蚀降解存在显著差异:凝胶在体内水分不断流失,无溶胀过程,注射4周后体内外凝胶的水含量分别为89%和97%;水分流失造成凝胶质量减小、结构致密、孔隙率平均降低17%。凝胶在体内与组织发生缔合,平均分子量明显大于体外,后随降解略有减小,但降解速率小于体外降解速率。上述体内外差异对指导体外试验、开展药物的控释研究有重要意义。Chitosan/glycerophosphate （CTS/GP） thermosensitive hydrogel has great potentials in injectable drug delivery and tissue engineering. The project of the present study is to explore the morphology and degradation of CTS/GP hydrogel in vitro （PBS） and in vivo （subcutaneousness of SD rat）. The pathological investigation shows that the CTS/GP hydrogel is enwrapped by a fiber capsule which can gradually attenuate, and the fiber tissue has the trend of inosculation with the hydrogel, which indicates that the CTS/GP hydrogel does not induce acute or chronic toxicity and is biological inertia. The effects of osmotic pressure, pH value, inflammation and tissue repair in vivo on CTS/GP hydrogel cause the significant differences in the morphology and degradation of CTS/GP hydrogel in vivo and in vitro. The inflammation and osmotic pressure lead dehydration on hydrogel, and its water content at 4 weeks after injection reduces to 89% in vivo, while the hydrogel undergoes a swelling process and its water content increases to 97% in vitro. Water loss of the hydrogel results in the more compact network structure and its porosity is 17% less than that in vitro. Due to the association and cross linking with the tissue, the Mw of the hydrogel experiences the trend of increasing at first, then slowly decreasing in vivo. The degradation rate of the CTS/GP hydrogel in vivo is slower than that in vitro. The experimental results are advisable for the design of injectable implant based on hydrogel.

关 键 词：壳聚糖 温敏水凝胶 降解 体内 释药 

分 类 号：R944.9[医药卫生—药剂学]