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

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 tamoxifenloaded nanoparticles (LCN-TAM) were assessed. The increase in the tamoxifen amount in the LCN-TAMpreparation 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 prolongedmanner. Tamoxifen-loaded nanoparticles showed cytotoxicity towardsMCF-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.