生物黏附型结肠靶向5-FU/癸酸钠微球用于门脉缓释化疗的研究

门静脉置管化疗存在与导管相关的诸多问题。近年研究（包括我们）提示结肠具有类似于"均质储药库"的特征，靶向结肠的药物呈现低水平的全身缓释性；而我们还发现，经口服结肠靶向释药系统给药也具有一定的门脉缓释性，但仍须大力优化。本项目拟在以往研究基础上，添加结肠粘膜促吸收剂癸酸钠，构建并筛选具有结肠靶向释药潜能的负载5-FU及癸酸钠的羧甲基壳聚糖/海藻酸钠微球，大鼠体内实验考察其结肠靶向性同时重点观察能否优化其门脉缓释性。鉴于新近研究提示生物粘附性修饰有利于其靶向药物更为恒定的结肠吸收，本项目拟进一步构建麦胚凝集素介导的粘附型结肠靶向5-FU/癸酸钠微球，大鼠体内观察能否进一步优化其门脉缓释性。本项目的成功实施，预期将为经口服途径给药进行门脉缓释化疗提供新思路，从而为常规"门脉化疗"提供另一可供选择的给药途径（或者成为它的有益补充）；同时也拓宽"结肠靶向系统"的应用范畴。

Intraportal venous chemotherapy (IPVC) probably leads to multiple catheter-related complications. Recent efforts, including ours, suggest that the colon has the characteristic of homogenous drug reservoir and colon-targeted drugs exhibit systemic sustained release at a low level. Moreover, we found the certain sustained release in portal venous system by the administration of oral colon-specific drug delivery system (OCDDS), but it should be further improved. Based on the former researches, incorporated with the colonic absorption enhancer sodium caprate, this study will be undertaken to synthesize and screen out carboxymethyl chitosan/sodium alginate microspheres loaded with 5-fluorouracil (5-FU) and sodium caprate characterized by certain potential colon-specific delivery in vitro, and then evaluate the property of colon-specific delivery and sustained release in portal venous system in rats. Considering the recent work that the incorporation of colonic mucoadhesion allows more consistent colonic mucosal uptake of colon-targeted drugs, the study will further synthesize wheat germ agglutinin-conjugated carboxymethyl chitosan/sodium alginate microspheres for local colon delivery of 5-FU and sodium caprate, and evaluate whether sustained-release profile in portal venous system could be further optimized in rats. The present investigation will offer new ideas for the sustained-release chemotherapy in portal venous system by oral administration and thus provide an alternative route of administration to conventional IPVC (or as a beneficial supplement to it), and meanwhile bring about new clinical implications for OCDDS.