In vitro evaluation of folate-modified PLGA nanoparticles containing paclitaxel for ovarian cancer therapy

Mater Sci Eng C Mater Biol Appl. 2019 Dec:105:110038. doi: 10.1016/j.msec.2019.110038. Epub 2019 Jul 30.

Abstract

Ovarian cancer is the most lethal gynecological cancer of female reproductive system. In order to improve the survival rate, some modifications on nanoparticles surfaces have been investigated to promote active targeting of drugs into tumor microenvironment. The aim of this study was the development and characterization of folate-modified (PN-PCX-FA) and unmodified PLGA nanoparticles (PN-PCX) containing paclitaxel for ovarian cancer treatment. Nanocarriers were produced using nanoprecipitation technique and characterized by mean particle diameter (MPD), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), DSC, FTIR, in vitro cytotoxicity and cellular uptake. PN-PCX and PN-PCX-FA showed MPD < 150 nm and PDI < 0.2 with high EE (about 90%). Cytotoxicity assays in SKOV-3 cells demonstrated the ability of both formulations to cause cellular damage. PCX encapsulated in PN-PCX-FA at 1 nM showed higher cytotoxicity than PN-PCX. Folate-modified nanoparticles showed a 3.6-fold higher cellular uptake than unmodified nanoparticles. PN-PCX-FA is a promising system to improve safety and efficacy of ovarian cancer treatment. Further in vivo studies are necessary to prove PN-PCX-FA potential.

Keywords: Active targeting; Chemotherapy; Folic acid; Nanocarrier; Ovarian cancer; Polymeric nanoparticles.

MeSH terms

  • Boron Compounds / chemical synthesis
  • Boron Compounds / chemistry
  • Calorimetry, Differential Scanning
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Endocytosis / drug effects
  • Female
  • Folic Acid / chemistry*
  • Humans
  • Nanoparticles / chemistry*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use*
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemical synthesis
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Folic Acid
  • Paclitaxel