Development and Characterization of PEGylated Chitosan Nanoparticles Co-loaded with Curcumin and Thymoquinone for Glioblastoma Therapy

Abstract

Glioblastoma multiforme (GBM) is an aggressive and therapy-resistant brain tumor, with treatment efficacy severely constrained by poor drug solubility, systemic toxicity, and the inability of conventional therapeutics to achieve sustained bioavailability. This study reports the development of a biocompatible PEGylated chitosan-based nanoparticle delivery system co-loaded with curcumin and thymoquinone, to address formulation and delivery barriers associated with these compounds. Nanoparticles were synthesized via ionotropic gelation and optimized for particle size, surface charge, and polydispersity index. PEGylation enhanced colloidal stability and reduced the zeta potential, thereby favoring systemic compatibility. High encapsulation efficiency and formulation yield

confirmed effective incorporation of both drugs, while UV-Vis spectroscopy validated successful co- loading. Comprehensive physicochemical characterization, using FTIR, FESEM, DLS, XRD, DSC,

and NMR, confirmed the integrity, amorphous dispersion, and thermal stability of the nanoparticles. The nanoparticle demonstrated excellent hemocompatibility, indicating suitability for systemic administration. The dual-drug formulation exhibited enhanced antibacterial activity against Staphylococcus aureus and Escherichia coli compared to single-drug nanoparticles, supporting synergistic bioactivity. In vitro cytotoxicity assays using LN229 glioblastoma cells revealed significantly higher anticancer activity of the dual-drug formulation relative to individual drug systems. Overall, this work highlights the potential of PEGylated chitosan nanoparticles co-delivering curcumin and thymoquinone for glioblastoma therapy