Solid lipid nanoparticles by coacervation loaded with a methotrexate prodrug: preliminary study for glioma treatment

Nanomedicine (Lond). 2017 Mar;12(6):639-656. doi: 10.2217/nnm-2016-0380. Epub 2017 Feb 10.

Abstract

Aim: Methotrexate-loaded biocompatible nanoparticles were tested for preliminary efficacy in glioma treatment.

Materials & methods: Behenic acid nanoparticles, prepared by the coacervation method, were loaded with the ester prodrug didodecylmethotrexate, which was previously tested in vitro against glioblastoma human primary cultures. Nanoparticle conjugation with an ApoE mimicking chimera peptide was performed to obtain active targeting to the brain.

Results & conclusion: Biodistribution studies in healthy rats assessed the superiority of ApoE-conjugated formulation, which was tested on an F98/Fischer glioma model. Differences were observed in tumor growth rate (measured by MRI) between control and treated rats. In vitro tests on F98 cultured cells assessed their susceptibility to treatment, with consequent apoptosis, and allowed us to explain the apoptosis observed in glioma models.

Keywords: ApoE; apoptosis; biodistribution; chimera peptide; coacervation; glioma; methotrexate; orthotopic model; solid lipid nanoparticles.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Glioma / drug therapy*
  • Humans
  • Lipids / administration & dosage
  • Lipids / chemistry
  • Methotrexate / administration & dosage*
  • Methotrexate / chemistry
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Prodrugs / administration & dosage*
  • Prodrugs / chemistry
  • Rats
  • Tissue Distribution

Substances

  • Drug Carriers
  • Lipids
  • Prodrugs
  • Methotrexate