Effect of metformin/irinotecan-loaded poly-lactic-co-glycolic acid nanoparticles on glioblastoma: in vitro and in vivo studies

Nanomedicine (Lond). 2018 Jul;13(13):1595-1606. doi: 10.2217/nnm-2017-0386. Epub 2018 Jul 20.

Abstract

Aim: The present study was designed to evaluate the effects of irinotecan hydrochloride (IRI)- or metformin hydrochloride (MET)-loaded poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for the treatment of glioblastoma multiforme using in vitro neuron and U-87 MG glioblastoma cell cultures and in vivo animal model.

Methods: The cytotoxic and neurotoxic effects of pure drugs, blank NPs and MET- and IRI-loaded PLGA NPs were investigated in vitro (using methylthiazolyldiphenyl-tetrazolium bromide assay) and in vivo (using Cavalieri's principle for estimation of cancer volume).

Results: 1 and 2 mM doses of MET and MET-loaded PLGA NPs, respectively, significantly reduced the volume of extracted cancer.

Conclusion: Consequently, MET- and IRI-loaded PLGA NPs may be a promising approach for the treatment of glioblastoma multiforme.

Keywords: Cavalieri's principle; PLGA; brain tumor; irinotecan; metformin; nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Irinotecan / administration & dosage*
  • Irinotecan / chemistry
  • Metformin / administration & dosage*
  • Metformin / chemistry
  • Microscopy, Electron, Transmission
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Neurons / drug effects
  • Neurons / pathology
  • Polylactic Acid-Polyglycolic Acid Copolymer / administration & dosage
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Rats

Substances

  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Irinotecan
  • Metformin