Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release

Int J Biol Macromol. 2023 Dec 31;253(Pt 2):126722. doi: 10.1016/j.ijbiomac.2023.126722. Epub 2023 Sep 8.

Abstract

Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) core-shell nanofiber webs were encapsulated with OL (PLAOL), rutin (PLArutin), and TMZ (PLATMZ) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core-shell structures with an average diameter between 133 ± 30.7-139 ± 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLAOL and PLATMZ suppressed GB cell viability with a controlled release that increased over 120 h, while PLArutin caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nano-webs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.

Keywords: Combined treatment; Glioblastoma local treatment; Nano-based drug delivery systems.

MeSH terms

  • Brain Neoplasms* / drug therapy
  • Cell Line, Tumor
  • Delayed-Action Preparations / pharmacology
  • Delayed-Action Preparations / therapeutic use
  • Glioblastoma* / drug therapy
  • Glioblastoma* / pathology
  • Humans
  • Nanofibers* / chemistry
  • Neoplasm Recurrence, Local
  • Polyesters / therapeutic use
  • Rutin / pharmacology
  • Temozolomide / pharmacology

Substances

  • Temozolomide
  • poly(lactide)
  • oleuropein
  • Delayed-Action Preparations
  • Rutin
  • Polyesters