title: Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: loading, enzyme-trigger release and cell uptake.
abstract: 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/100 ml 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 20mg. 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.
authors: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors: Stefano
authors: S
authors: Barbieri
authors: Fabio
authors: F
authors: Sonvico
authors: Caterina
authors: C
authors: Como
authors: Gaia
authors: G
authors: Colombo
authors: Franca
authors: F
authors: Zani
authors: Francesca
authors: F
authors: Buttini
authors: Ruggero
authors: R
authors: Bettini
authors: Alessandra
authors: A
authors: Rossi
authors: Paolo
authors: P
authors: Colombo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001692:Biological Transport; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D005750:Gastric Juice / Q000737:chemistry; D006801:Humans; D007419:Intestinal Secretions / Q000737:chemistry; D054709:Lecithins / Q000737:chemistry*; D008049:Lipase / Q000737:chemistry; D061986:MCF-7 Cells; D009113:Muramidase / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010194:Pancreatin / Q000737:chemistry; D011374:Progesterone / Q000737:chemistry; D013629:Tamoxifen / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D054709:Lecithins; D013629:Tamoxifen; D011374:Progesterone; D010194:Pancreatin; D048271:Chitosan; D008049:Lipase; D009113:Muramidase