Doxorubicin Hydrochloride-loaded Nanoparticles for Oral Delivery: Optimization using Design of Experiments

Abstract

Doxorubicin hydrochloride (DOX) has low oral bioavailability due to the presence of active efflux from intestinal P-glycoprotein receptors. Because of the difficulties associated with the oral administration of DOX, there is not yet a commercially available oral formulation of DOX. Nanocarrier system was manufactured utilizing poly (lactic-co-glycolic acid) (PLGA) and treated with chitosan to provide a surface coated. Nanoparticles (NPs) were created using a modified emulsification solvent diffusion (nanoprecipitation) method by electrostatic conjugation of chitosan to modify nanoparticle surfaces. The model was built using a Box-Behnken design with three independent components: X1 (PLGA), X2 (poloxamer 188), and X3 (chitosan concentration). The optimized chitosan-PLGA NPs had a mean particle size of 153.6 nm and a positive zeta potential of 21.51 mV. More than 85% DOX permeated through the everted gut by DOX-loaded chitosan-NPs as compared to NPs prepared with PLGA alone. Chitosan nanoparticles caused a 6-fold increase in DOX intestinal permeability. The findings pointed to the possibility of using chitosan-based nanoparticles of doxorubicin for oral treatment for cancer.