Lin Wen-Jen, Wang Chia-Ling, Chen Yi-Chen
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Drug Deliv. 2005 Jul-Aug;12(4):223-7. doi: 10.1080/10717540590952672.
The aim of this study was to evaluate the ability of forming micelles from two types of synthesized diblock pegylated amphiphilic copolymers and their potential as a drug carrier. Two lactone monomers, epsilon-caprolactone (CL) and delta-valerolactone (VL), were copolymerized with methoxy poly(ethylene glycol) (MePEG), respectively. The properties of copolymers were investigated and their biocompatibility was tested through an in vitro cytotoxicity study. The influences of the type of lactone monomer (CL and VL) and the feed molar ratios of lactone/MePEG (50/1, 80/1, 160/1) on the performance and release behavior of drug-loaded micelles were investigated. The opening of CL and VL rings by MePEG was efficient, and the pegylation of poly(lactone)s allowed copolymers possessing amphiphilic property and efficiently self-assembled to form micelles with a low critical micelle concentration (CMC) in the range of 10(-7)-10(-8) M. The nano-sized micelles were able to incorporate hydrophobic drug and regulate drug release, and the release of drug was dominated by the hydrophobic poly(lactone) chain length. Although both amphiphilic copolymers exhibited similar controlled release character, the PCL/MePEG micelles possessed lower CMC, higher biocompatibility, and higher drug loading than PVL/MePEG micelles. These suggested that results choosing pegylated PCL as a drug carrier could be better than PVL/MePEG.
本研究的目的是评估两种合成的二嵌段聚乙二醇化两亲共聚物形成胶束的能力及其作为药物载体的潜力。两种内酯单体,ε-己内酯(CL)和δ-戊内酯(VL),分别与甲氧基聚(乙二醇)(MePEG)共聚。研究了共聚物的性质,并通过体外细胞毒性研究测试了它们的生物相容性。研究了内酯单体类型(CL和VL)以及内酯/MePEG的进料摩尔比(50/1、80/1、160/1)对载药胶束性能和释放行为的影响。MePEG使CL和VL环开环的反应很有效,聚(内酯)的聚乙二醇化使共聚物具有两亲性,并能有效自组装形成临界胶束浓度(CMC)低至10(-7)-10(-8)M的胶束。纳米尺寸的胶束能够包载疏水性药物并调节药物释放,药物的释放主要受疏水性聚(内酯)链长度的影响。尽管两种两亲共聚物都表现出相似的控释特性,但PCL/MePEG胶束比PVL/MePEG胶束具有更低的CMC、更高的生物相容性和更高的载药量。这些结果表明,选择聚乙二醇化PCL作为药物载体可能比PVL/MePEG更好。