注射用紫杉醇聚合物胶束稳定性的研究

目的:从聚合物胶束动力学稳定性机制出发,研究制备温度及贮存温度对以PLA-mPEG为载体的紫杉醇聚合物胶束物理稳定性的影响。方法:通过DSC法考察PLA-mPEG疏水嵌段的玻璃化温度,通过荧光偏振法、荧光光谱法及1H-NMR谱图分别考察PLA-mPEG疏水嵌段粘度、极性及其链段移动性随温度的变化;采用熔融蒸发法制备紫杉醇聚合物胶束,建立了以T1和K为参数的紫杉醇胶束稳定性考察方法,并考察其在不同制备及贮存温度下物理稳定性的变化。结果:在玻璃化温度附近,PLA-mPEG聚合物胶束疏水嵌段的粘度较小,核嵌段迁移较剧烈,极性较大;而通过熔融蒸发法制备的紫杉醇载药聚合物胶束在玻璃化温度附近,即50℃下水化后物理稳定性较好,贮存温度在4℃物理稳定性较好,符合基于紫杉醇载药聚合物胶束微观性质的结果对其物理稳定性的预测。结论:聚合物胶束动力学稳定性的机理,对制备稳定的紫杉醇载药胶束有着重要的指导意义。

Effect of polyoxypropylene chain length on the critical micelle concentration of propylene oxide-ethylene oxide block copolymers

In this work, the surface activity of block copolymer nonionic surfactants (RPE) has been determined, i.e., critical micelle concentration (CMC), surface excess concentration (Γ), surface area demand per molecule (A), surface tension at CMC (γCMC). A linear decrease of ln[CMC] vs number of oxypropylene units in copolymer molecule was observed. The change in the work of cohesion per oxypropylene group when passing from molecular into micellar state, calculated from the Shinoda equation, was 0.43kT for the studied compounds.