A thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of docetaxel
A thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of docetaxel
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DOI：
10.3109/1061186x.2010.519031
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发表时间：
2011-08-01
影响因子：
4.5
通讯作者：
Gao, Shen
中科院分区：
文献类型：
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作者：
Gao, Yuan;Ren, Fuzheng;Gao, Shen
本研究的目的是研究聚（D，L-乳酸-羟基乙酸）（PLGA）-聚乙二醇（PEG）-PLGA三嵌段共聚物作为多西他赛（DTX）缓释系统基质材料的适用性。通过开环聚合反应合成了共聚物，并用核磁共振氢谱和凝胶渗透色谱对共聚物进行了表征。制备并表征了负载有DTX的制剂。研究了载药共聚物对A-549荷瘤BALB/cA小鼠的抗肿瘤作用及药代动力学。结果表明，DTX负载共聚物大大提高了DTX的溶解度超过3000倍。共聚物浓度和载药量对药物释放行为有明显影响。药物动力学实验表明，载药共聚物具有3周以上的缓释性质，与体外释放度相关性良好。此外，在抑制A-549肺荷瘤BALB/cA小鼠中的肿瘤生长方面，一次瘤内注射含有DTX的热敏性水凝胶与三次静脉注射DTX注射液相当，毒性较低。因此，PLGA-PEG-PLGA可以为DTX提供有希望的替代局部递送载体，以实现延长的暴露，在抑制肿瘤生长方面具有更大的功效和更低的毒性。
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 H-1-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 thermosensitive 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.