Gold nanoparticles for sustained antileukemia drug release: development, optimization and evaluation by quality-by-design approach

Nanomedicine (Lond). 2019 Apr;14(7):851-870. doi: 10.2217/nnm-2018-0306. Epub 2019 Mar 22.

Abstract

Aim: To design, develop, optimize and evaluate sustained-release dasatinib-loaded gold nanoparticles (DSB-GNPs) to treat chronic myeloid leukemia (CML) by using quality by design.

Materials & methods: In this study, we performed risk assessment, optimization, in vitro characterizations, stability study, drug release studies, cytotoxicity study and in vivo pharmacokinetic evaluation.

Results: DSB-GNPs of desired size, entrapment, smooth, spherical, stable and sustained drug release for 48 h were achieved. DSB-GNPs exhibited significantly more percentage growth inhibition and enhanced systemic bioavailability compared with pure DSB.

Conclusion: The in vitro and in vivo evaluation exhibited that the DSB-GNPs have a potential cytotoxic effect, systemic bioavailability and sustained release making them a promising system of DSB delivery in the treatment of chronic myeloid leukemia.

Keywords: chronic myeloid leukemia; cytotoxicity study; dasatinib; full factorial design; gold nanoparticles; quality by design; risk assessment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Biocompatible Materials / chemistry
  • Biological Availability
  • Cell Survival / drug effects
  • Dasatinib / chemistry*
  • Dasatinib / pharmacokinetics
  • Delayed-Action Preparations / chemistry*
  • Delayed-Action Preparations / pharmacokinetics
  • Drug Carriers / chemistry*
  • Drug Compounding / methods
  • Drug Liberation
  • Drug Stability
  • Female
  • Gold / chemistry*
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Male
  • Metal Nanoparticles / chemistry*
  • Particle Size
  • Rats, Sprague-Dawley
  • Risk Assessment
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • Delayed-Action Preparations
  • Drug Carriers
  • Gold
  • Dasatinib