Glycyrrhizin conjugated chitosan nanoparticles for hepatocyte-targeted delivery of lamivudine

J Pharm Pharmacol. 2014 Aug;66(8):1082-93. doi: 10.1111/jphp.12235. Epub 2014 Mar 19.

Abstract

Objective: The present study was focused to prepare controlled release glycyrrhizin (GL) conjugated low molecular weight chitosan nanoparticles (CS-NPs) for liver targeting. The hydrophilic antiretroviral drug lamivudine was chosen as a model drug and encapsulated within glycyrrhizin conjugated low molecular weight chitosan nanoparticles (GL-CS-NPs) for liver specificity.

Methods: First, the low molecular weight chitosan (CS) was synthesized through depolymerization method. The low molecular weight chitosan nanoparticles were prepared by inotropic gelation method. Then glycyrrhizin was conjugated with previously prepared low molecular weight chitosan nanoparticles (CS-NPs) and conjugation was confirmed by Fourier transform infrared (FT-IR) spectroscopy.

Key findings: The prepared GL-CS-NPs were characterized using dynamic light scattering, transmission electron microscopy and FT-IR. The encapsulation efficiency and in-vitro drug release behaviour of drug-loaded GL-CS-NPs were studied using ultra violet spectroscopy and high performance liquid chromatographic methods. Release of lamivudine from the nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. In-vivo biodistribution study suggested the target ability of GL-CS-NPs is better and haematological study shows decline of the tissue damage in comparison with plain drug solution.

Conclusion: The experimental results show that the glycyrrhizin conjugated LMWC nanoparticles may be used as a potential drug delivery system with hepatocyte-targeting characteristics.

Keywords: chitosan; glycyrrhizin; lamivudine; liver targeting.

MeSH terms

  • Animals
  • Anti-Retroviral Agents / chemistry
  • Chitosan / chemistry*
  • Delayed-Action Preparations / chemistry
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Glycyrrhizic Acid / chemistry*
  • Hepatocytes / drug effects*
  • Lamivudine / chemistry*
  • Molecular Weight
  • Nanoparticles / chemistry*
  • Particle Size
  • Rats
  • Tissue Distribution

Substances

  • Anti-Retroviral Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Lamivudine
  • Glycyrrhizic Acid
  • Chitosan