Preparation and optimization of glyceryl monooleate-low molecular weight chitosan nanoparticles for delivery of morpholinopyrrolizine derivative

Abstract

Purpose: To develop and optimize glyceryl monooleate–low-molecular-weight chitosan (GMO-LMWC) nanoparticles loaded with morpholinopyrrolizine derivative (NPM). Methods: Molecular mechanics was used to determine the main driving force for the complexation between glyceryl monooleate (GMO) and chitosan. Nanoparticles were fabricated using a modified film-rehydration method. Optimization was carried out using a statistical design approach. The effects of formulation factors (concentrations of GMO, LMWC and Tween 80) on zeta potential and particle size were investigated using a 23 factorial design. Results: A steady increase in binding energy was observed when chitosan length was increased from 22 to 142 Å, and thereafter it remained almost constant. The examined independent variables had significant effects on particle size and zeta potential. The particle size of the nanoparticles varied from 265 to 1270 nm while zeta potential was in the range of 3 – 12 mV. The optimized preparation showed a significantly low half-maximal inhibitory concentration (IC50) when compared to a free anticancer agent in the hepatocellular carcinoma (HePG-2) cell line. Conclusion: A nanoparticulate system composed of GMO and LMWC is a potential nanocarrier for delivery of morpholinopyrrolizine derivative.