PLA/PLGA nanoparticles for sustained release of docetaxel
PLA/PLGA nanoparticles for sustained release of docetaxel
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DOI：
10.1016/j.ijpharm.2006.06.023
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发表时间：
2006-11-15
影响因子：
5.8
通讯作者：
Puglisi, G.
中科院分区：
文献类型：
--
作者：
Musumeci, T.;Ventura, C. A.;Puglisi, G.
本研究考察了纳米球胶体混悬液作为静脉注射多西紫杉醇(DTX)缓释系统的可能性。以不同相对分子质量的聚乳酸(PLA)和聚乳酸-羟基乙酸(PLGA)为生物可降解基质，采用溶剂置换法制备了纳米微球。用光散射分析了它们的平均尺寸、粒径分布和Zeta电位，并用扫描电子显微镜(SEM)对其表面形貌进行了表征。纳米粒子的平均直径在100~200 nm之间。所有体系的Zeta电位值都为负，特别是以最低相对分子质量的聚乳酸制备的纳米球的Zeta电位值为-28 mV。差示扫描量热分析(DSC)表明DTX以分子形式分散在聚合物基质中。所有胶体混悬液都观察到DTX的两相释放，在释放约50%(w/w)的负载药物的突释效应后，观察到约10天的缓释曲线。为了评价聚合物载体对DTX与生物膜相互作用的影响，我们以二棕榈酰磷脂酰胆碱(DPPC)制成的脂泡为生物膜模型进行了体外研究。差示扫描量热法是一种简单、非侵入性的分析技术。DTX使DPPC的预相变峰降低，主相变温度无明显变化，Delta H值显著升高，表明药物对DPPC双层有表面渗透作用。动力学实验表明，DTX从纳米球中释放的过程受所用聚合物的相对分子质量的影响。(C)2006年，爱思唯尔出版。
This study investigates the potentiality of nanosphere colloidal suspensions as sustained release systems for intravenous administration of docetaxel (DTX). Nanospheres were prepared by solvent displacement method using polylactic acids (PLA) at different molecular weight and polylactic-co-glycolic (PLGA) as biodegradable matrices. The systems were characterized by light scattering analysis for their mean size, size distribution and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The average diameters of the nanoparticles ranged from 100 to 200 nm. Negative zeta potential values were observed for all systems, particularly the nanospheres produced with the lowest molecular weight PLA showed a zeta potential value of -28 mV. Differential scanning calorimetry analysis (DSC) suggested that DTX was molecularly dispersed in the polymeric matrices. A biphasic release of DTX was observed for all colloidal suspensions, after a burst effect in which about 50% (w/w) of the loaded drug was released a sustained release profile for about 10 days was observed. To evaluate the influence of the polymeric carrier on the interaction of DTX with biological membranes, we performed an in vitro study using lipid vesicles made of dipalmitoylphosphatidylcholine (DPPC) as a biomembrane model. DSC was used as a simple and not invasive technique of analysis. DTX produced a depression of DPPC pretransition peak, no variation of the main phase transition temperature and a significative increase of Delta H value, showing a superficial penetration of the drug into DPPC bilayer. Kinetic experiments demonstrated that the release process of DTX form nanospheres is affected by the molecular weight of the employed polymers. (c) 2006 Published by Elsevier B.V.