Abstract

Cerebral toxoplasmosis is a significant cause of morbidity and mortality, especially in immunocompromised individuals, with treatment hindered by poor drug bioavailability in the brain, systemic side effects, and relapse risk. This study aimed to develop an effective nose-to-brain therapeutic strategy using poly (ε-caprolactone) nanoparticles loaded with trimethoprim and sulfamethoxazole and coated with chitosan. Trimethoprim and sulfamethoxazole and coated with chitosan were synthesized, optimized, and coated with 0.5 % CS. Trimethoprim and sulfamethoxazole and coated with chitosan were characterized using analytical techniques, and their in vitro drug release and efficacy against Toxoplasma gondii-infected rat primary astrocytes were evaluated. For in vivo studies, trimethoprim and sulfamethoxazole and coated with chitosan were labeled with IR820, administered intranasally to mice, and their biodistribution was monitored in live animals to assess nose-to-brain delivery. TMP-SMX-NPsCS showed 174 nm, a 0.14 polydispersity index, and +31 mV zeta potential. Encapsulation efficiencies were 88.93 % for TMP and 85.23 % for SMX. FTIR and thermal analysis confirmed uniform drug dispersion and successful CS coating. In vitro drug release studies showed sustained release of both drugs over 24 hours under simulated nasal conditions. trimethoprim and sulfamethoxazole and coated with chitosan treatment maintained 72% cell viability compared to untreated controls. In vivo imaging and ex vivo analysis in mice confirmed brain accumulation and limited systemic distribution of IR820-labeled trimethoprim and sulfamethoxazole and coated with chitosan after intranasal administration. These findings suggest that intranasal delivery of trimethoprim and sulfamethoxazole and coated with chitosan is a promising strategy for expanding the therapeutic arsenal against cerebral toxoplasmosis by enabling direct drug delivery to the brain.