Indomethacin-Encapsulated PLGA Nanoparticles Improve Therapeutic Efficacy by Increasing Apoptosis and Reducing Motility in Glioblastoma Cells

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 (160.6nm), 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 ⁓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 200mM, IC50 value of free-IND (treatment- time:48h) was 390mM. Furthermore, IND/PLGA-NPs’ anticancer activity (100mM 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.