可注射更昔洛韦温敏型原位凝胶剂的研究

构建温敏型三嵌段共聚物，研究其理化性质以及用其制备的可注射更昔洛韦温敏型原位凝胶剂的制剂特性。以聚乙二醇（PEG）作为亲水嵌段．丙交酯（LA）和β-丁内酯（β-BL）的无规共聚物PBLA作为疏水嵌段．采用开环聚合法合成温敏型三嵌段共聚物PBLA-PEG-PBLA，并对其理化性质进行表征，考察其溶液的胶凝温度／临界凝胶浓度、流变学性质、通针性和溶蚀行为以及以更昔洛韦作为模型药物、用其制得的可注射载药温敏型原位凝胶剂的体外释放特性。合成的PBLA-PEG-PBLA嵌段共聚物重均分子质量在6000左右，多分散系数为1．5左右；其溶液临界凝胶浓度（g·mL^-1）为5％-10％，质量浓度（g·mL^-1）在10％～25％时胶凝温度为31～35℃，接近并略低于体温：其凝胶在低温下储能模量与黏度较小，当温度接近相转变温度后两者迅速增大：其载药凝胶剂累计释放量经拟合显示遵循一级动力学方程，并呈扩散释药机制。较低质量浓度10％15％（g·mL^-1）的PBLA—PEG—PBLA更符合玻璃体注射要求，更适用于制备可注射载药温敏型原位凝胶剂。

Study on Injectable Thermosensitive In-situ Hydrogel as Ganciclovir Delivery System

To construct thermosensitive triblock copolymer and to investigate its physicochemical properties and the characteristics of the injectable therrnosensitive in-situ hydrogel as ganciclovir （GCV） delivery system prepared with the copolyrner. A thermosensitive PBLA-PEG-PBLA triblock copolymer was synthesized with polyethylene glycol （PEG） as the hydrophilic block and PBLA random copolymer comprising lactide（LA） and β-butyrolacton（β-BL） as the hydrophobic block by ring-opening polymerization. Its physicochemical properties were characterized as well as the gelation temperature/critical gel concentration, rheological property, syringeability and dissolution behavior of its solution and in vitro release property of the drug-loaded injectable thermosensitive in-situ hydrogel prepared with GCV as a model drug and the copolymer were investigated. The average molecular weight （M_w） of the synthesized PBLA-PEG-PBLA copolymer was about 6 000 with a narrow potydispersity （PDI） of approximate 1.5. The critical gel concentration （g·mL^-1）of its solution was between 5% to 10% and gelation temperature oF its solution was about 31-35 ℃ which was slightly lower than body temperature at the concentration（g·mL^-1） range of 10%-25%. The storage modulus and viscosity of the hydrogel solution were low （below T_s-g）, but could increase rapidly when temperature reached T,.：. The cumulative release curve of the drug-loaded hydrogel followed the one-order kinetics with a diffusion-release mechanism. Low concentrations（10%-15% g·mL^-1） of PBLA-PEG-PBLA copolymer conforms more completely to the requirements of intravitreous injection of copolymers and is applicable to the preparation of the drug-loaded injectable tbermosensitive in-situ hydrogel.