Danhier Fabienne, Lecouturier Nathalie, Vroman Benoît, Jérôme Christine, Marchand-Brynaert Jacqueline, Feron Olivier, Préat Véronique
Université Catholique de Louvain, Unité de Pharmacie Galénique, Avenue Mounier, 73-20, 1200 Brussels, Belgium.
J Control Release. 2009 Jan 5;133(1):11-7. doi: 10.1016/j.jconrel.2008.09.086. Epub 2008 Oct 9.
The purpose of this study was to develop Cremophor EL-free nanoparticles loaded with Paclitaxel (PTX), intended to be intravenously administered, able to improve the therapeutic index of the drug and devoid of the adverse effects of Cremophor EL. PTX-loaded PEGylated PLGA-based were prepared by simple emulsion and nanoprecipitation. The incorporation efficiency of PTX was higher with the nanoprecipitation technique. The release behavior of PTX exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release. The in vitro anti-tumoral activity was assessed using the Human Cervix Carcinoma cells (HeLa) by the MTT test and was compared to the commercial formulation Taxol and to Cremophor EL. When exposed to 25 microg/ml of PTX, the cell viability was lower for PTX-loaded nanoparticles than for Taxol (IC(50) 5.5 vs 15.5 microg/ml). Flow cytometry studies showed that the cellular uptake of PTX-loaded nanoparticles was concentration and time dependent. Exposure of HeLa cells to Taxol and PTX-loaded nanoparticles induced the same percentage of apoptotic cells. PTX-loaded nanoparticles showed greater tumor growth inhibition effect in vivo on TLT tumor, compared with Taxol. Therefore, PTX-loaded nanoparticles may be considered as an effective anticancer drug delivery system for cancer chemotherapy.
本研究的目的是开发负载紫杉醇（PTX）的无聚氧乙烯蓖麻油（Cremophor EL）纳米颗粒，旨在用于静脉给药，能够提高药物的治疗指数并避免聚氧乙烯蓖麻油的不良反应。通过简单乳液法和纳米沉淀法制备了负载PTX的聚乙二醇化聚乳酸-羟基乙酸共聚物（PLGA）纳米粒。纳米沉淀技术对PTX的包封效率更高。PTX的释放行为呈现双相模式，其特征是初始的突释随后是较慢的持续释放。通过MTT试验，使用人宫颈癌细胞（HeLa）评估体外抗肿瘤活性，并与市售制剂紫杉醇以及聚氧乙烯蓖麻油进行比较。当暴露于25μg/ml的PTX时，负载PTX的纳米颗粒的细胞活力低于紫杉醇（IC50分别为5.5和15.5μg/ml）。流式细胞术研究表明，负载PTX的纳米颗粒的细胞摄取具有浓度和时间依赖性。HeLa细胞暴露于紫杉醇和负载PTX的纳米颗粒诱导的凋亡细胞百分比相同。与紫杉醇相比，负载PTX的纳米颗粒在体内对TLT肿瘤显示出更大的肿瘤生长抑制作用。因此，负载PTX的纳米颗粒可被视为癌症化疗的一种有效的抗癌药物递送系统。
