Development and characterization of L-HSA conjugated PLGA nanoparticle for hepatocyte targeted delivery of antiviral drug

The present study demonstrates preparation and characterization of polymeric nanoparticles (NPs) conjugated with Lactosaminated-Human Serum Albumin (L-HSA) peptide. Ligand L-HSA was targeted to Asialoglycoprotein-Receptors (ASGP-R) overexpressed on parenchymal cell surface of hepatocytes. Poly (lactic-co-glycolic acid) PLGA NPs surface functionalized with maleimide group were formulated using Interfacial Activity Assisted Surface Functionalization (IAASF) technique. The hydrophilic antiretroviral drug lamivudine was encapsulated into PLGA NP using double emulsion solvent evaporation technique for liver specificity. A Central Composite Design (CCD) was applied to optimize maleimide functionalized PLGA NP formulation parameters and studied its effect on particle size and encapsulation efficiency. The optimized batch was conjugated with L-HSA. Inclusion of maleimide group was confirmed by FTIR, 1H-NMR, and conjugation of L-HSA to the PLGA NP was confirmed by SDS-PAGE, in vitro cell uptake, in vivo pharmacokinetic and biodistribution studies. L-HSA conjugation resulted in 2.17 fold increase in cell uptake and 3.84 fold longer retention in HepG2 cells. The in vivo pharmacokinetic and biodistribution study revealed higher AUC and efficient target ability of L-HSA conjugated NP in mice liver compared to other organs. These results concluded that proposed L-HSA conjugated maleimide functionalized PLGA NP can be used as promising hepatocyte targeted drug delivery system for Lamivudine.