Pure antiestrogen RU 58668-loaded nanospheres: morphology, cell activity and toxicity studies

被引:24
作者
Ameller, T [1 ]
Marsaud, W [1 ]
Legrand, P [1 ]
Gref, R [1 ]
Renoir, JM [1 ]
机构
[1] CNRS, UMR 8612, F-92296 Chatenay Malabry, France
关键词
nanospheres; antiestrogen; morphology; cell activity;
D O I
10.1016/j.ejps.2003.11.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Nanospheres, (NS) formulated using biodegradable and biocompatible polymers, poly(D,L-lactide-co-glycolide) (PLGA), poly(D,L-lactide) (PLA) and poly(epsilon-caprolactone) (PCL), loaded with the pure anti-estrogen RU 58668 (RU), a promising estrogen-dependent anticancer agent, have been prepared. They all possess a small size compatible with an intratumoral extravasation behavior and their pegylation reduce significantly their zeta potential. Characterization by freeze fracture electron microscopy have shown that NS are spheric particles with a size ranging between 30 and 50 nm and a tendency to agglomerate which is reduced by polyethylene glycol (PEG) grafting. PEG-grafted NS are all non-toxic as revealed by cell viability assay. A specific cellular model has been used to evaluate not only the release extent of the drug but also its biological activity. All formulations tested showed that they release slowly RU as measured by the delayed ability of RU to inhibit estrogen-induced transcription in human breast cancer cells and that they possess only a small amount of surface adsorbed RU. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码:361 / 370
页数:10
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