Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China.
J Drug Target. 2011 Aug;19(7):516-27. doi: 10.3109/1061186X.2010.519031. Epub 2010 Sep 30.
The aim of this study was to investigate the suitability of poly-(d,l-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymer as a matrix material for a sustained-release system for docetaxel (DTX). The copolymers were synthesized by ring-opening polymerization reaction and characterized by (1)H-NMR and gel permeation chromatography. The DTX-loaded formulations were prepared, characterized. And the antitumor efficacy and the pharmacokinetics of DTX-loaded copolymer on A-549 lung tumor-bearing BALB/cA mice were investigated. The results showed that DTX-loaded copolymer highly increased the solubility of DTX by more than 3000-fold. And copolymer concentration as well as drug loading level exerted appreciable influence on the drug release behavior. Further, the pharmacokinetic test showed that DTX-loaded copolymer could be with the sustained-release nature for over 3 weeks, which correlated well with the in vitro release. Additionally, one intratumoral injection of the thermo-sensitive hydrogel containing DTX was comparable to three intravenous injections of DTX injection in inhibiting the tumor growth in A-549 lung tumor-bearing BALB/cA mice with a less toxic manner. PLGA-PEG-PLGA could thus provide a promising alternate locally delivered vehicle for DTX to achieve prolonged exposure having greater efficacy in inhibiting tumor growth with lower toxicity.
本研究旨在探讨聚（丙交酯-乙交酯）（PLGA）-聚乙二醇（PEG）-PLGA 三嵌段共聚物作为多西紫杉醇（DTX）缓释系统基质材料的适用性。通过开环聚合反应合成共聚物，并通过（1）H-NMR 和凝胶渗透色谱进行表征。制备并表征了 DTX 载体制剂，并研究了载药共聚物在 A-549 肺癌荷瘤 BALB/cA 小鼠中的抗肿瘤功效和药代动力学。结果表明，载药共聚物使 DTX 的溶解度提高了 3000 多倍以上。共聚物浓度和载药量对药物释放行为有明显影响。进一步的药代动力学试验表明，载药共聚物具有超过 3 周的缓释特性，与体外释放情况相符。此外，载有 DTX 的温敏水凝胶的一次瘤内注射在抑制 A-549 肺癌荷瘤 BALB/cA 小鼠肿瘤生长方面与 DTX 注射液的三次静脉注射相当，且具有较低的毒性。PLGA-PEG-PLGA 可为 DTX 提供一种有前途的局部递药载体，以实现延长暴露，从而具有更高的抗肿瘤生长疗效和更低的毒性。
