The effect of Pluronic on the protein release kinetics of an injectable drug delivery system
The effect of Pluronic on the protein release kinetics of an injectable drug delivery system
复制标题
DOI：
10.1016/s0168-3659(02)00293-6
复制
发表时间：
2003-01-09
影响因子：
10.8
通讯作者：
McHugh, AJ
中科院分区：
文献类型：
--
作者：
DesNoyer, JR;McHugh, AJ
通过加入在相变过程中优先分离的材料，已经制备了一种新型的可注射控制释放库。其中包括聚环氧乙烷(PEO)/聚环氧丙烷(PPO)/聚氧乙烯(PEO)三嵌段共聚物(Pluronics)与聚(D，L-丙交酯)(PDLA)/1-甲基-2-吡咯烷酮(NMP)溶液的共混。利用暗衬底成像、高效液相色谱(HPLC)、扫描电子显微镜(SEM)和共聚焦显微镜研究了择优偏析对相转化动力学和体外蛋白质释放动力学的影响。Pluronic浓度和相对分子质量的变化对内部储存库的形态影响不大，然而，增加浓度和相对分子质量确实会导致相分离率增加，令人惊讶的是，蛋白质爆发的幅度降低，尽管释放谱仍然保持典型的爆发型形状。此外，增加Pluronic浓度超过临界点会导致从爆破型到缓释型的转变。用蛋白质释放机制的定性模型对这些结果进行了解释。(C)2002 Elsevier Science B.V.保留所有权利。
A new class of injectable controlled release depots has been prepared by incorporating materials that preferentially segregate during phase inversion. These consist of blends of poly(ethylene oxide) (PEO)/poly(propylene oxide) (PPO)/ poly(ethylene oxide) (PEO) triblock copolymers (Pluronics) with poly(D,L-lactide) (PDLA)/1-methyl-2- pyrrolidinone (NMP) solutions. The effects of preferential segregation on the phase inversion dynamics and in vitro protein release kinetics were examined using dark ground imaging, high performance liquid chromatography (HPLC), scanning electron microscopy (SEM), and confocal microscopy. Variations in Pluronic concentration and molecular weight had an insignificant effect on the internal depot morphologies, however, increasing the concentration and molecular weight did result in increased phase separation rates and, surprisingly, a decrease in the magnitude of the protein burst, though the release profiles still retained a typical burst-type shape. Additionally, increasing the Pluronic concentration beyond a critical point resulted in a transition from a burst-type profile to an extended-release profile. An interpretation of these results in terms of a qualitative model for the protein release mechanism is also given. (C) 2002 Elsevier Science B.V. All rights reserved.