Preferential hepatic uptake of paclitaxel-loaded poly-(d-l-lactide-co-glycolide) nanoparticles - A possibility for hepatic drug targeting: Pharmacokinetics and biodistribution

Int J Biol Macromol. 2018 Jun:112:818-830. doi: 10.1016/j.ijbiomac.2018.02.021. Epub 2018 Feb 5.

Abstract

Liver cancer is a leading cause of death related to cancer worldwide. Poly(d-l-lactide-co-glycolide) (PLGA) nanoparticles provide prolonged blood residence time and sustained drug release, desirable for cancer treatment. To achieve this, we have developed paclitaxel-loaded PLGA nanoparticles by emulsification solvent evaporation method and evaluated by in vitro and in vivo studies. The results obtained from in vitro study showed that drug loading efficiency was 84.25% with an initial burst release followed by sustained drug release. Cellular uptake and in vitro cytotoxicity of the formulated nanoparticles using HepG2, Huh-7 cancer cells and Chang liver cells were also investigated. The formulated nanoparticles showed more cytotoxic effect at lower concentration and were internalized well by HepG2 cells compared to free-drug and marketed formulation. Prolonged half-life and higher plasma and liver drug concentrations of the formulated nanoparticles were observed as compared to free drug and marketed formulation in rats. Thus, paclitaxel-loaded polymeric nanoparticle has shown its potential for the treatment of liver cancer.

Keywords: Cytotoxicity; HepG2 cells; Liver cancer; Paclitaxel; Pharmacokinetics; Poly-(d-l-lactide-co-glycolide) nanoparticles.

MeSH terms

  • Animals
  • Calorimetry, Differential Scanning
  • Cell Survival / drug effects
  • Drug Delivery Systems*
  • Drug Liberation
  • Endocytosis / drug effects
  • Hep G2 Cells
  • Humans
  • Hydrolysis
  • Kinetics
  • Lactic Acid / chemistry*
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Malondialdehyde / metabolism
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Paclitaxel / administration & dosage
  • Paclitaxel / blood
  • Paclitaxel / pharmacokinetics*
  • Paclitaxel / pharmacology
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats, Sprague-Dawley
  • Spectroscopy, Fourier Transform Infrared
  • Static Electricity
  • Tissue Distribution / drug effects

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Malondialdehyde
  • Paclitaxel