Estradiol loaded PLGA nanoparticles for oral administration:: Effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo
Estradiol loaded PLGA nanoparticles for oral administration:: Effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo
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DOI：
10.1016/j.jconrel.2007.01.016
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发表时间：
2007-05-14
影响因子：
10.8
通讯作者：
Kumar, M. N. V. Ravi
中科院分区：
文献类型：
--
作者：
Mittal, G.;Sahana, D. K.;Kumar, M. N. V. Ravi
本研究旨在优化雌二醇负载PLGA纳米颗粒制剂，通过改变PLGA的分子量和共聚物组成，改善雌二醇的口服生物利用度和缓释。以十二烷基二甲基溴化铵（DMAB）为稳定剂，采用乳化-扩散-蒸发法制备纳米粒子。已经报道了聚合物分子量和共聚物组成对颗粒性质和释放行为（体外和体内）的影响。药物的体外释放随PLGA分子量和丙交酯含量的增加而降低。用低分子量（14，500和45，000 Da）PLGA获得零级释放，而高分子量（85，000和213，000 Da）和不同共聚物组合物遵循时间平方根（Higuchi模式）依赖性释放。在雄性Sprague道利（SD）大鼠中以1 mg雌二醇/大鼠的剂量评估来自纳米颗粒的雌二醇的生物利用度。发现纳米颗粒的体内性能取决于粒径、聚合物分子量和共聚物组成。药物在血浆中的C-max取决于聚合物的分子量和组成，而发现粒径影响释放持续时间，表明越小越好。组织病理学检查显示，在研究期间，由低/高分子量或高丙交酯含量聚合物制备的制剂没有任何炎症反应。总之，这些结果表明，纳米颗粒制剂是用于雌二醇口服给药的理想载体，具有解决雌二醇剂量相关问题的巨大潜力。(c)2007 Elsevier B. V.保留所有权利。
The present investigation was aimed at optimization of estradiol loaded PLGA nanoparticulate formulations resulting in improved oral bioavailability and sustained release of estradiol by varying the molecular weight and copolymer composition of PLGA. Nanoparticles were prepared following emulsion-diffusion-evaporation method employing didodecyldimethyl ammonium bromide (DMAB) as stabilizer. The effect of polymer molecular weight and copolymer composition on particle properties and release behavior (in vitro and in vivo) has been reported. Drug release in vitro decreased with increase in molecular weight and lactide content of PLGA. Zero order release was obtained with low molecular weight (14,500 and 45,000 Da) PLGA, while high molecular weight (85,000 and 213,000 Da) and different copolymer compositions followed square root of time (Higuchi's pattern) dependent release. The bioavailability of estradiol from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg estradiol/rat. The in vivo performance of the nanoparticles was found to be dependent on the particle size, polymer molecular weight and copolymer composition. The C-max of drug in the plasma was dependent on the polymer molecular weight and composition while particle size was found to influence the duration of release, suggesting smaller is better. The histopathological examination revealed absence of any inflammatory response with the formulations prepared of low/high molecular weight or high lactide content polymers for the studied period. Together, these results indicate that nanoparticulate formulations are ideal carriers for oral administration of estradiol having great potential to address the dose related issues of estradiol. (c) 2007 Elsevier B.V. All rights reserved.