基于树枝状嵌段共聚物的载药微球的制备及其药物释放表征

Preparation and Properties of Microsphere Carriers Based on Biodegradable Comb-Dendritic Tri-Block Copolymers in Controlled Drug Release

为建立一种树枝状共聚物载药微球的制备方法及其药物释放行为的体外评价机制,研究采用实验室自制的4代树枝状大分子引发剂PEG-G4-(OH)32引发己内酯开环聚合,合成了一系列树枝状三嵌段共聚物,并对其结构进行了表征;采用乳液-溶剂挥发法制备了共聚物-紫杉醇载药微球。研究结果显示,以树枝状嵌段共聚物为壁材的载药微球形貌规整,表面平滑,粒径范围为1.92～2.54μm,载药量为15.7%～20.6%;在0～3d的时间里载药微球释药明显,在随后的3～15d的时间里基本呈现线性的零级释放效果。该研究首次采用树枝化聚己内酯的嵌段共聚物制备载药微球,与以线性聚己内酯为壁材制备的载药微球进行了对比,结果表明,前者药物缓释效果更好,具有一定的临床应用前景。

To develop methods for the preparation of drug loaded microspheres using dendritic copolymers and evaluation of drug release behaviour in vitro, serious of comb-dendritic tri-block copolymers have been synthesized by ring opening polymerization of caprolactone in the presence of a macromolecular initiator PEG-G4-（OH）32. The structures of the copolymers have been characterized. A standard oil-in-water （o/w） emulsion solvent evaporation method was used to fabricate microspheres entrapping paclitaxel using the above copolymers. The obtained microspheres showed smooth surface and spherical size in the range over 1.92-2. 54 μm, and the drug loading content varied from 15. 7% to 20. 6%, depending on the polymer structures. Their paclitaxel release curves were nearly linear,indicating zero-order release kinetics in 3-15 days after an initial relative quick release in the first 3 days. For the first time, this study appllied the dendrintic copolumers to prepare microspheres loading paclitaxel. In comparison with the microspheres prepared from linear PCL, the microspheres using dendritic copolymers showed a better drug releasing profile in the prospect of clinical applications.