Comparison of temozolomid-loaded formulations prepared by nanoprecipitation and double emulsion solvent evaporation methods in terms of effectiveness and target selectivity

Treatment options for glioblastoma multiforme (GBM) remain highly limited. As one of the most lethal primary brain tumors, GBM presents significant therapeutic challenges. Although temozolomide (TEM) is the standard chemotherapeutic agent used in GBM treatment, its clinical efficacy is severely hampered by rapid systemic clearance, low brain penetration, and non-selective cytotoxicity. In this study, two innovative oral TEM delivery systems based on PLGA nanoparticles (NPs) were developed and comparatively evaluated using 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, release kinetics, and solid-state analysis (DSC and FTIR)—confirmed the successful formation of nanosystems with favorable properties. The NP1-TEM formulation, prepared via nanoprecipitation, demonstrated superior features compared to the NP2-TEM formulation obtained via the double emulsion technique, including smaller particle size, narrower size distribution, higher encapsulation efficiency, and more efficient cellular uptake. Furthermore, cytotoxicity studies conducted on U-87 MG glioblastoma and NIH/3T3 fibroblast cell lines revealed enhanced tumor selectivity and elevated reactive oxygen species (ROS) generation for NP1-TEM, highlighting its potential for selective tumor targeting. The findings of this thesis study indicate that optimized nanoencapsulation significantly improves the release and therapeutic performance of TEM, offering a promising strategy for the next generation of GBM treatments.