Dual functional chitosan-coated spanlastics for topical delivery of ceftazidime in the treatment of bacterial burn wound infections.

Burn wound infections (BWIs) remain a significant cause of morbidity and mortality due to persistent biofilms, enzymatic antibiotic degradation, and limited drug penetration. To address these challenges, a dual-functional nanoplatform of ceftazidime-loaded chitosan-coated spanlastics embedded in a carbopol hydrogel (CCNP-G) was developed. Molecular docking revealed favorable interactions of chitosan with keratin and weaker binding with AmpC β-lactamase, suggesting its role in bio adhesion and protection of ceftazidime (CFZ), while ceftazidime demonstrated strong binding to penicillin-binding protein 3 (PBP3). Ceftazidime-loaded spanlastics (CNP) were prepared by thin-film hydration and optimized using a Box-Behnken design, then coated with chitosan via electrostatic adsorption. Physicochemical characterization of CCNP showed a particle size of 368.8 ± 3.5 nm, zeta potential of +38.1 ± 4.8 mV, and entrapment efficiency of 88 ± 2.22 %. Fourier transform infrared (FTIR) analysis confirmed absence of chemical interactions, X-ray diffration (XRD) indicated successful conversion from crystalline to amorphous form, and scanning electron microscopy (SEM) revealed spherical morphology. In vitro studies demonstrated sustained drug release, while ex vivo permeation studies confirmed enhanced drug penetration and skin retention. In vivo evaluation in rats burn wound model showed accelerated wound healing, significant reduction in bacterial burden, downregulation of pro-inflammatory cytokines, and superior histopathological recovery compared to marketed 1 % silver sulfadiazine cream USP. Collectively, CCNP-G represents a dual-functional therapeutic platform that combines the antimicrobial and biofilm-disrupting properties of chitosan with the penetration and sustained release benefits of spanlastics within a hydrogel matrix, offering a clinically relevant strategy for effective burn wound infection management.