Aqueous Dispersion Polymerization for the Development of Lamivudine-Polyacrylonitrile Nanoparticles through Quality by Design Approach.

Abstract

The development of polymeric nanoparticles (NPs) from preformed polymers usually requires the use of organic solvents and is more expensive. Hence, in this work, the development of polymeric nanoparticles by in situ aqueous dispersion polymerization from the monomers was set as an objective. Acrylonitrile monomer based polymeric NPs comprising Lamivudine (LMV) as a model drug were prepared using the aqueous dispersion polymerization technique. A quality by design approach was applied to optimise various formulation and process factors viz. monomer concentration, initiator concentration, stabilizer concentration and polymerization temperature. Polymerization time (PT), entrapment efficiency (EE), particle size (PS), and drug release rate constant (k) were taken as the responses to define the quality of the prepared NPs. Design of experiments analysis followed by optimization was performed to identify the optimized combination of the factors. Later, the optimized formulation was studied for the physical state of the LMV in the nanoparticles, surface morphology of the NPs and cytotoxicity studies. The optimized formulation was found to have 91.7 min. of PT, 81.4% of EE, 253 nm of PS and a k value of 0.262 h-1 (18 h to release 99%). The cytotoxicity studies indicated that the NPs were highly safe to use. These results altogether inferred that LMV contained NPs were developed effectively from the acrylonitrile monomer by the aqueous dispersion polymerization method.