Anti-cancerous efficacy and pharmacokinetics of 6-mercaptopurine loaded chitosan nanoparticles

Pharmacol Res. 2015 Oct:100:47-57. doi: 10.1016/j.phrs.2015.07.025. Epub 2015 Jul 29.

Abstract

6-Mercaptopurine is a cytotoxic and immunosuppressant drug. The use of this drug is limited due to its poor bioavailability and short plasma half-life. In order to nullify these drawbacks, 6-mercaptopurine-chitosan nanoparticles (6-MP-CNPs) were prepared and evaluated to study the influence of preparation conditions on the physicochemical properties by using DLS, SEM, XRD and FTIR. The in vitro drug release profile at pH 4.8 and 7.4 revealed sustained release patterns for a period of 2 days. The nanoformulations showed enhanced in vitro anti-cancer activities (MTT assay, apoptosis assay, cell cycle arrest and ROS indices) on HT-1080 and MCF-7 cells. In vivo pharmacokinetics profiles of 6-MP-CNPs showed improved bioavailability. Thus, the results of the present study revealed that, the prepared 6-MP-CNPs have a significant role in increasing anti-cancer efficacy, bioavailability and in vivo pharmacokinetics profiles.

Keywords: Apoptosis; Chitosan nanoparticles; Cytotoxic; ROS and bioavailability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Biological Availability
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Chitosan / administration & dosage*
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Drug Carriers / administration & dosage
  • Drug Delivery Systems / methods
  • Humans
  • MCF-7 Cells
  • Mercaptopurine / pharmacokinetics*
  • Mercaptopurine / pharmacology*
  • Nanoparticles / administration & dosage*
  • Particle Size

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Chitosan
  • Mercaptopurine