The effect of temozolomide/poly(lactide-co-glycolide) (PLGA)/nano-hydroxyapatite microspheres on glioma U87 cells behavior

Int J Mol Sci. 2012;13(1):1109-1125. doi: 10.3390/ijms13011109. Epub 2012 Jan 19.

Abstract

In this study, we investigated the effects of temozolomide (TMZ)/Poly (lactide-co-glycolide)(PLGA)/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the "Solid/Water/Oil" method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning calorimetry. The proliferation, apoptosis and invasion of glioma cells were evaluated by MTT, flow cytometry assay and Transwell assay. The presence of the key invasive gene, α(V)β3 integrin, was detected by the RT-PCR and Western blot method. It was found that the temozolomide/PLGA/nano-hydroxyapatite microspheres have a significantly diminished initial burst of drug release, compared to the TMZ laden PLGA microspheres. Our results suggest they can significantly inhibit the proliferation and invasion of glioma cells, and induce their apoptosis. Additionally, α(V)β3 integrin was also reduced by the microspheres. These data suggest that by inhibiting the biological behavior of glioma cells in vitro, the newly designed temozolomide/PLGA/nano-hydroxyapatite microspheres, as controlled drug release carriers, have promising potential in treating glioma.

Keywords: Poly (lactide-co-glycolide) PLGA; controlled release; glioma; hydroxyapatite; temozolomide (TMZ).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / chemistry*
  • Antineoplastic Agents, Alkylating / toxicity
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / chemistry
  • Dacarbazine / toxicity
  • Drug Carriers / chemistry
  • Durapatite / chemistry*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Lactic Acid / chemistry*
  • Microspheres*
  • Nanostructures / chemistry*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Temozolomide

Substances

  • Antineoplastic Agents, Alkylating
  • Drug Carriers
  • Integrin alphaVbeta3
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Dacarbazine
  • Durapatite
  • Temozolomide