Celecoxib–Phospholipid Conjugate Loaded Nanostructured Lipid Carriers for Enhanced Brain Delivery in Seizure Treatment

Purpose Epilepsy, characterized by recurrent seizures, remains a global health challenge, especially with drug-resistant epilepsy affecting 30% of patients. Neuroinflammation is pivotal in epileptogenesis, with Cyclooxygenase-2 (COX-2) being a significant therapeutic target. While celecoxib, a COX-2 inhibitor, shows anticonvulsant potential, its systemic side effects and limited brain-targeting efficacy necessitate the development of novel delivery strategies. This study explores nanostructured lipid carriers (NLCs) to enhance the effectiveness and safety of celecoxib-phospholipid conjugates. Methods Celecoxib–phospholipid conjugate NLCs were optimized using a Box–Behnken design and characterized for particle size, entrapment efficiency, release profile, and stability. Biocompatibility was assessed in SH-SY5Y neuroblastoma cells and goat nasal mucosa, while anticonvulsant efficacy was evaluated in a pentylenetetrazol-induced zebrafish seizure model. Results Optimized NLCs (particle size ~ 273 nm, entrapment efficiency ~ 91%) demonstrated sustained drug release (78% in 48 h) and excellent stability. Ex vivo and in vitro studies confirmed safety with no cytotoxicity. Zebrafish larvae treated with conjugate-loaded NLCs showed a significant reversal of seizure-like behavior compared with conjugate alone, confirming enhanced antiepileptic efficacy. Conclusion Celecoxib–phospholipid conjugate NLCs provide a safe and effective brain-targeted delivery system with potential for clinical translation in drug-resistant epilepsy.