Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia

Mol Pharm. 2017 Mar 6;14(3):722-732. doi: 10.1021/acs.molpharmaceut.6b01008. Epub 2017 Feb 16.

Abstract

The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia.

Keywords: acute lymphoblastic leukemia (ALL); micelle; nanoparticle; parthenolide; pluronic; poloxamer.

MeSH terms

  • Biocompatible Materials / chemistry
  • Cells, Cultured
  • Drug Carriers / chemistry*
  • Drug Stability
  • Emulsions / chemistry
  • Humans
  • Mesenchymal Stem Cells / drug effects
  • Micelles
  • Polymers / chemistry*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / pharmacology*
  • Solubility
  • Solvents / chemistry

Substances

  • Biocompatible Materials
  • Drug Carriers
  • Emulsions
  • Micelles
  • Polymers
  • Sesquiterpenes
  • Solvents
  • parthenolide