Preparation and evaluation of temozolomide loaded PLGA nanoparticles for the treatment of glioblastoma multiforme

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Şahin Ş., Kaya Tilki E., Baysal M., Öztürk A. A.

SCIENTIFIC REPORTS, vol.15, pp.1-22, 2025 (SCI-Expanded, Scopus) identifier

  • Publication Type: Article / Article
  • Volume: 15
  • Publication Date: 2025
  • Doi Number: 10.1038/s41598-025-20012-x
  • Journal Name: SCIENTIFIC REPORTS
  • Journal Indexes: Scopus, Science Citation Index Expanded (SCI-EXPANDED), Academic Search Premier, BIOSIS, Chemical Abstracts Core, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.1-22
  • Open Archive Collection: AVESIS Open Access Collection
  • Anadolu University Affiliated: Yes

Abstract

Glioblastoma multiforme (GBM) remains one of the most lethal primary brain tumors, with limited

treatment options and poor patient prognosis. Although temozolomide (TMZ) is the standard

chemotherapeutic agent for GBM, its clinical efficacy is severely hindered by rapid systemic clearance,

low brain penetration, and non-selective cytotoxicity. In this study, we developed and comparatively

evaluated two innovative PLGA-based nanoparticle (NP) systems for oral TMZ delivery, prepared

via nanoprecipitation and double emulsion solvent evaporation techniques. Comprehensive

physicochemical characterization, including particle size, polydispersity index (PDI), zeta potential

(ZP), encapsulation efficiency (EE%), in vitro release kinetics, and solid-state analysis (DSC and

FTIR), demonstrated the successful formation of nanosystems with favorable properties. NP1-TMZ

(nanoprecipitation) showed superior characteristics, including smaller particle size, narrower size

distribution, higher encapsulation efficiency, and more efficient cellular uptake compared to NP2-TMZ

(double emulsion). Moreover, cytotoxicity studies in U-87 MG glioblastoma and NIH/3T3 fibroblast

cell lines revealed enhanced tumor selectivity and reactive oxygen species (ROS) generation for NP1-

TMZ, highlighting its potential for selective tumor targeting. Our results demonstrate that optimized

nanoencapsulation significantly improves TMZ delivery, stability, and therapeutic performance,

offering a promising strategy for next-generation GBM treatments.