Development and characterization of cationic solid lipid nanoparticles for co-delivery of pemetrexed and miR-21 antisense oligonucleotide to glioblastoma cells

Drug Dev Ind Pharm. 2018 Feb;44(2):306-315. doi: 10.1080/03639045.2017.1391835. Epub 2017 Nov 2.

Abstract

The practical use of solid lipid nanoparticles (SLNs) in research has been highlighted in the literature, but few reports have combined SLNs with miRNA-based therapy and chemotherapy. We aimed to prepare cationic SLNs (cSLNs) to load anti-miR-21 oligonucleotide and pemetrexed for glioblastoma therapy in vitro. cSLNs were employed to encapsulate both pemetrexed and anti-miR-21 by a high-pressure homogenization method, and then the properties of cSLNs were characterized. We studied cellular uptake and cytotoxicity properties of cSLNs in U87MG cells. cSLNs were 124.9 ± 1.6 nm in size and 27.3 ± 1.6 mV in zeta potential with spherical morphology in the TEM image. cSLNs uptake by U87MG cells was increased significantly higher and more effective than free pemetrexed. These findings suggest that cSLNs represent a potential new approach for carrying both pemetrexed and anti-miR-21 for glioblastoma therapy.

Keywords: Pemetrexed; anti-miRNA oligonucleotide; glioblastoma; microRNA-21; solid lipid nanoparticles.

MeSH terms

  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods
  • Chromatography, High Pressure Liquid
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Glioblastoma / drug therapy*
  • Humans
  • Lipids / chemistry
  • MicroRNAs
  • Nanoparticles / chemistry*
  • Oligonucleotides, Antisense / administration & dosage*
  • Oligonucleotides, Antisense / pharmacology*
  • Particle Size
  • Pemetrexed / administration & dosage*
  • Pemetrexed / pharmacology*
  • Surface Properties

Substances

  • Lipids
  • MIRN21 microRNA, human
  • MicroRNAs
  • Oligonucleotides, Antisense
  • Pemetrexed