SOLID LIPID NANOPARTICLES FOR ORAL DELIVERY OF SILIBININ: FORMULATION, CHARACTERIZATION AND EVALUATION USING PAMPA AND CACO-2 CELL MODELS

The study is focused on the preparation and evaluation of naked and chitosan-coated solid lipid nanoparticles (SLNs) containing silibinin (Sb) to increase its intestinal absorption. Sb is the key biologically active flavonolignan present in silymarin isolated from the fruits and seed of Silybum marianum L. Gaertn. (Asteracee). Sb is used for treatment of liver toxicities, inflammation, fibrosis, oxidative stress and different carcinomas. Recently Sb has been proposed to be beneficial in type 2 diabetes patients. However, its hydrophobicity nature limits bioavailability compromising in vivo biological effects [1]. In this work SLNs were prepared by emulsion/evaporation/solidifying method, using stearic acid and brij 78. In order to improve the delivery efficacy of SLNs we applied a chitosan coating. Based on cationic property chitosan-coated nanoparticles exhibit mucoadhesive features and prolonged residence time in small intestine, thus increasing the drug concentration at the site of absorption [2]. Developed SLNs exhibited particle size and z potential in the range of 150 – 200nm and -48 – +40 mV respectively. Encapsulation efficiency and recovery were greater than 90%. Moreover SLNs showed excellent stability in both simulated gastric fluid and simulated intestinal fluid with a small release of Sb during at least 24 hours. Further we demonstrated that SLNs were successful in increasing the permeation of Sb by Parallel Artificial Membrane Permeability Assay (PAMPA). Fluorescein isothiocyanate was selected as a model dye to analyse in vitro uptake and permeation of drug using Caco-2 cells. The cell line studies revealed higher uptake and apparent permeability of fluorescent-SLNs than free probe. The obtained results suggest that the developed SLNs could improve the bioavailability of Sb.