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

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• 作者：Stefano Barbieri^a ; ¹ ; ² ; Fabio Sonvico^a ; ² ; ³ ; Caterina Como^a ; ² ; ⁴ ; Gaia Colombo^b ; Franca Zani^a ; Francesca Buttini^a ; Ruggero Bettini^a ; Alessandra Rossi^a ; Paolo Colombo^a ; ^{farmac2@unipr.it}
• 关键词：Tamoxifen citrate ; Chitosan ; Lecithin ; Nanoparticles ; Lysozyme ; Caco-2
• 刊名：Journal of Controlled Release
• 出版年：2013
• 出版时间：10 May, 2013
• 年：2013
• 卷：167
• 期：3
• 页码：276-283
• 全文大小：954 K

文摘

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 physico-chemical 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.