Indomethacin-encapsulated PLGA nanoparticles improve therapeutic efficacy by increasing apoptosis and reducing motility in glioblastoma cells


Pekmez M., Bostancı F., Şengelen A., Aksüt Y., Yıldırım E., Öğütçü İ., ...More

PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, vol.10, no.1, pp.1-12, 2025 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 10 Issue: 1
  • Publication Date: 2025
  • Doi Number: 10.1080/10837450.2024.2448333
  • Journal Name: PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Business Source Elite, Business Source Premier, Chemical Abstracts Core, International Pharmaceutical Abstracts, MEDLINE
  • Page Numbers: pp.1-12
  • Istanbul University Affiliated: Yes

Abstract

Glioblastoma, with a low survival rate, is an aggressive and difficult-to-treat lethal type of brain cancer. Indomethacin (IND), a non-steroidal anti-inflammatory drug, has antitumoral activity in many cancers, including gliomas. However, its poor aqueous solubility is a critical issue. Nanomaterials are crucial tools for overcoming solubility problems and facilitating drug delivery. Herein, a polymeric nanoparticle system, poly(lactic-co-glycolic acid) (PLGA) was used to encapsulate IND. Although PLGA is an FDA-approved copolymer for drug delivery, no trials with IND-loaded PLGA-NPs have been conducted to treat brain tumors. Encapsulation success was revealed by DLS, zeta potential, TEM, and FTIR analysis; IND/PLGA-NPs had nanoscale particle size (160.6 nm), narrow size distribution (0.230, PDI), and good stability (-23.9 mV). Fluorescence imaging showed that PLGA-NPs can penetrate U-87MG cells. Short-term/one-hour treatment with bound-IND increased the free-IND effect in gliomas by similar to 10 times/48h and 12.39 times/72h. Even against long-term exposure to IND, IND/PLGA-NP treatment revealed a highly marked result; the IC50 value of bound-IND (treatment-time:1h, analysis at 48h) was similar to 200 mu M, IC50 value of free-IND (treatment-time:48h) was similar to 390 mu M. Furthermore, IND/PLGA-NPs' anticancer activity (100 mu M of IND/1h, analysis at 48h) was also supported by induced apoptosis and reduced migration/colony formation in glioma cells. All evidence suggests that IND/PLGA-NPs may be a potentially promising agent for treating gliomas.