Co-encapsulation of superparamagnetic nanoparticles and doxorubicin in PLGA nanocarriers: Development, characterization and in vitro antitumor efficacy in glioma cells

Eur J Pharm Biopharm. 2019 Dec:145:65-75. doi: 10.1016/j.ejpb.2019.10.004. Epub 2019 Oct 16.

Abstract

With a very poor prognosis and no clear etiology, glioma is the most aggressive cancer in the brain. Thanks to its versatility, nanomedicine is a promising option to overcome the limitations on chemotherapy imposed by the blood brain barrier (BBB). The objective of this paper was to obtain monitored tumor-targeted therapeutic nanoparticles (NPs). To that end, theranostic surfactant-coated polymer poly-Lactic-co-Glycolic Acid (PLGA) nanoplatform encapsulating doxorubicin hydrochloride (DOX) and superparamagnetic iron oxide NPs (SPIONs) were developed. Different non-ionic surfactants known as BBB crossing enhancers (Tween 80, Brij-35, Pluronic F68 or Vitamin E-TPGS) were used to develop 4 types of theranostic nanoplatforms, which were characterized in terms of size and morphology by DLS, TEM and STEM-HAADF analyses. Moreover, the 3-month stability test, the therapeutic efficacy against different glioma cell lines (U87-MG, 9L/LacZ and patient derived-neuronal stem cells) and the Magnetic Resonance Imaging (MRI) relaxivity were studied. Results showed that the synthesised nanoplatforms were stable at 4 °C after their lyophilization, being that of paramount importance to ensure a long-term stability in a future in vivo application. Furthermore, the theranostic nanoplatforms were efficient in the in vitro treatment of glioma cells, proving to have imaging efficacy as MRI contrast agents. Our results show an efficient loading of drugs and good value of the relaxivity. Therefore, the efficient theranostic hybrid nanoplatform developed here could be used to perform MRI-guided delivery of hydrophobic drugs.

Keywords: 9L/LacZ; Brij- 35; Neurospheres; PVA; Pluronic F68; SPION; Tween 80; U87-MG; Vitamin E-TPGS.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Cell Line
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry*
  • Drug Carriers / chemistry*
  • Drug Delivery Systems / methods
  • Glioma / drug therapy*
  • Humans
  • Magnetite Nanoparticles / chemistry*
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Rats
  • Surface-Active Agents / chemistry

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Magnetite Nanoparticles
  • Surface-Active Agents
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Doxorubicin