Lactoferrin functionalized PEG-PLGA nanoparticles of shikonin for brain targeting therapy of glioma

Int J Biol Macromol. 2018 Feb;107(Pt A):204-211. doi: 10.1016/j.ijbiomac.2017.08.155. Epub 2017 Aug 31.

Abstract

Shikonin (SHK) is a highly liposoluble naphthoquinone pigment has recently been investigated as a potential antiglioma agent. However, shikonin shows several limitations like poor aqueous solubility, short half-life and non-selective biodistribution. Herein, we have developed a nanoparticles (NPs) prepared from PEG-PLGA using an emulsion solvent evaporation method. Nanoparticle surfaces were modified by coating with lactoferrin (Lf) to improve the crossing of the blood brain barrier and targeting of glioma cells via receptor-mediated path-ways. X-ray powder diffraction and differential scanning calorimetry analysis revealed the amorphous nature of SHK encapsulated within the NPs. Moreover, the drug-loaded NPs exhibit narrow size distribution and high encapsulation efficiency. The in vitro release experiments of the NPs exhibited sustained release for more than 72h. When compared to free SHK and SHK/NPs, in vivo study demonstrated higher brain concentration of SHK, indicating a significant effect of Lf coated NPs on brain targeting. Accordingly, these findings provide evidence for the potential of Lf-modified NPs as a targeted delivery system for brain glioblastomas treatment.

Keywords: Glioma; Nanoparticles; Shikonin.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / pathology
  • Cell Line, Tumor
  • Drug Carriers / administration & dosage
  • Drug Carriers / adverse effects
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Glioma / drug therapy*
  • Humans
  • Lactoferrin / administration & dosage
  • Lactoferrin / adverse effects
  • Lactoferrin / chemistry*
  • Nanoparticles / administration & dosage
  • Nanoparticles / adverse effects
  • Nanoparticles / chemistry*
  • Naphthoquinones / administration & dosage
  • Naphthoquinones / adverse effects
  • Naphthoquinones / chemistry*
  • Naphthoquinones / therapeutic use
  • Polyesters / administration & dosage
  • Polyesters / adverse effects
  • Polyesters / chemistry
  • Polyesters / therapeutic use
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / therapeutic use
  • Rats
  • Tissue Distribution

Substances

  • Drug Carriers
  • Naphthoquinones
  • Polyesters
  • polyethylene glycol-poly(lactide-co-glycolide)
  • shikonin
  • Polyethylene Glycols
  • Lactoferrin