Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: Loading, enzyme-trigger release and cell uptake

被引:63
作者
Barbieri, Stefano [1 ]
Sonvico, Fabio [1 ]
Como, Caterina [1 ]
Colombo, Gaia [2 ]
Zani, Franca [1 ]
Buttini, Francesca [1 ]
Bettini, Ruggero [1 ]
Rossi, Alessandra [1 ]
Colombo, Paolo [1 ]
机构
[1] Univ Parma, Dept Pharm, I-43124 Parma, Italy
[2] Univ Ferrara, Dept Life Sci & Biotechnol, I-44121 Ferrara, Italy
关键词
Tamoxifen citrate; Chitosan; Lecithin; Nanoparticles; Lysozyme; Caco-2; ORAL CHEMOTHERAPY; NANOPARTICLES; CHITOSAN; DELIVERY; THERAPY; DRUGS;
D O I
10.1016/j.jconrel.2013.02.009
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Tamoxifen citrate (TAM), an anticancer drug with amphiphilic properties, was loaded in lecithin/chitosan nanoparticles (LCN) with a view to oral administration. The influence of tamoxifen loading on the physicochemical properties of nanoparticles was studied. Size, surface charge and morphological properties of tamoxifen-loaded nanoparticles (LCN-TAM) were assessed. The increase in the tamoxifen amount in the LCN-TAM preparation up to 60 mg/100ml maintained the positive zeta potential value of about +45 mV. A statistically significant decrease in particle size was observed for TAM amounts between 5 and 20 mg. A strong influence of loaded tamoxifen on the structure of lecithin/chitosan nanoparticles was observed, supported by the quantification of free chitosan and morphological analysis. A loading of tamoxifen in nanoparticles of around 19% was obtained. The release of the drug from the LCN-TAM colloidal dispersion was measured, showing that tamoxifen citrate was released very slowly in simulated gastro-intestinal fluids without enzymes. When enzymes able to dismantle the nanoparticle structure were added to the dissolution medium, drug release was triggered and continued in a prolonged manner. Tamoxifen-loaded nanoparticles showed cytotoxicity towards MCF-7 cells comparable to that obtained with tamoxifen citrate solution, but the rate of this toxic effect was dependent on drug release. Caco-2 cells, used as a model of the intestinal epithelium, were shown to take up the TAM loaded nanoparticles extensively. (C) 2013 Elsevier B. V. All rights reserved.
引用
收藏
页码:276 / 283
页数:8
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