Tamoxifen loaded auto-assembled nanoparticles for oral delivery: cytotoxicity and peremeability studies

The purpose of this study was to characterise and study on cell cultures chitosan/lecithin nanoparticles loaded with tamoxifen (TAM-NCL). The mucoadhesion and the permeation through excised rat intestinal mucosa of the nanoparticles was also investigated TAM-NCL were prepared by injection of methanol solution of lecithin and TAM in a chitosan solution. Cytotoxicity was investigated by MTT test using CaCo-2 and MCF-7 cells at different times and using different concentrations of TAM-NCL. The permeation studies through rat intestinal mucosa were performed in ex-vivo experiments using the Ussing chambers. The TAM-NCL cytotoxicity experiments towards MCF-7 cells showed that only after 24 or 48 h cells viability was reduced. This is in accordance with previous drug release data in which the release of TAM from nanoparticles occurred only when enzymes degraded nanoparticle components. Concerning the permeation trough the intestinal wall, nanoparticles slightly increased tamoxifen permeation compared to a control suspension of tamoxifen. However using enzymes able to degrade specifically the components of the nanoparticles (i.e. lipase contained in pancreatin) the tamoxifen flux trough the intestinal mucosa increased significantly. This increase was negated if a dialysis membrane is interposed as a barrier separating the nanoparticles from the mucosal surface. The permeation experiments on rat intestinal tissue showed then that mucoadhesion and enzymatic degradation of nanocarriers are required to increase the drug flux through the rat intestinal mucosa when chitosan/lecithin nanoparticles are employed as drug delivery system.