Dipali M.Dhoke
Rashtrasant Tukadoji Maharaj Nagpur University, India.
Title: A novel method to incorporate maleimide functional groups and HSA peptide on polymeric nanoparticles for hepatocyte-targeted delivery of lamivudine
Biography
Biography: Dipali M.Dhoke
Abstract
Targeted delivery of a wide variety of payloads can be achieved using nanoparticles formulated using poly(D,L-lactide-co-glycolide)PLGA as a copolymer which has emerged as a most promising nanocarrier. However, PLGA nanoparticles (NPs) have limited types of functional groups available on the surface for conjugation to targeting ligands which is its important drawback. In this study the interfacial activity assisted surface functionalization (IAASF) technique can be used to incorporate reactive functional groups such as maleimide onto the surface of PLGA NPs. This maleimide group can be further linked with lactosaminated Human Serum Albumin (L-HSA) which acts as a ligand and target the asialoglycoprotein receptor (ASGPR) present in large amounts and with high affinity on hepatocytes. The ligand bound functionalized NPs were formulated by solvent evaporation method and optimized using Central Composite design. The incorporation of maleimide group and HSA was confirmed by FTIR, NMR, SDS-PAGE, in vitro cell uptake study and in vivo biodistribution study. The functionalized NPs were further characterized using dynamic light scattering, TEM, DSC and XRD. The encapsulation efficiency, in-vitro drug release behaviour and in vivo studies of drug-loaded-NPs were studied using ultra violet spectroscopy and HPLC methods. The functionalized NPs showed a burst release at beginning and sustained release until 24 h in physiological conditions. Functionalization of NPs with L-HSA peptide increased the cellular uptake of NPs 2-3-fold, and this enhancement in uptake was substantially reduced in the absence of the ligand. In-vivo biodistribution study suggested the enhanced target ability and accumulation of surface functionalized ligand bound NPs. In conclusion, the IAASF technique enabled the incorporation of reactive maleimide groups on PLGA NPs, which in turn permitted efficient conjugation of biologically active L-HSA peptide to the surface of PLGA NPs. Nucleoside analogs (NAs) like lamivudin when loaded in NPs conjugated with galactosyl terminating peptides selectively enter hepatocytes via the ASGPR and thus reduce the extrahepatic side effects of lamivudin in the treatment of chronic viral hepatitis.