Preparation and in vitro characterization of lamivudine loaded nanoparticles prepared by acid and/or ester terminated PLGA for effective oral anti-retroviral therapy

Abstract

The aim of this study was to formulate Lamivudine (LAM) loaded poly lactic-co-glycolic acid (PLGA)nanoparticle (NP) formulations by ‘double emulsion solvent evaporation’ method for oral administration. PLGA withsimilar molecular weight but two different chemical end-groups (acid or ester terminated), were used in this study toto compare the effects in the characterization of NPs. Particle size (PS), polydispersity index (PDI), zeta potential,entrapment efficiency (EE%), dissolution and release kinetic studies were carried out for the characterization of NPsand finally for determining the optimum formulation. The selected optimum formulation (B coded) was found to havea PS of 221.00.7 nm and a low PDI as 0.1040.014. Drug EE % of optimal NP formulation was found as 30.280%0.600.In vitro release of LAM loaded NPs were examined in phosphate buffer (pH 6.8). In vitro release studies of LAM-loadedNPs showed an extended release up to 144 hours, thus the demonstration of nanostructures was confirmed. Higuchiand Korsmeyer-Peppas kinetic model was found to fit best for LAM release from PLGA-NPs. The optimum formulationwas stable in the 24-hour gastrointestinal stability study and the NP structure was characterized by DSC, FT-IR and 1HNMRanalyzes. It could be concluded that LAM loaded NPs seem to be a promising extended release drug deliverysystem for oral administration in antiretroviral therapy. Lastly, in vitro characterization and release data demonstratedthe possibility of improved bioavailability of LAM by PLGA-NP formulation and the effect of polymers used in thisstudy on formulation characteristics were also elucidated