Optimized curcumin-loaded anionic niosomes for intranasal delivery: enhanced ex vivo nasal permeation and cytotoxicity against neuroblastoma

Aims To develop and evaluate a Quality-by-Design (QbD) optimized curcumin-loaded niosomal (OptCUR-NS) formulation for intranasal delivery and determine its delivery performance and in vitro activity against neuroblastoma.Materials and methods A D-optimal design was used to optimize the Span 60:cholesterol ratio, Span 60:dicetyl phosphate ratio, and curcumin concentration. OptCUR-NS was characterized for vesicle properties, solid-state behavior, release, ex vivo nasal permeation, endothelial transport, cytotoxicity in SK-N-SH and SH-SY5Y cells, cellular uptake, cell-cycle distribution, migration, and cytocompatibility in F-180 fibroblasts.Results OptCUR-NS showed a particle size of 133.57 nm, surface charge of −48.16 mV, and entrapment efficiency of 62.05%. It exhibited biphasic release and increased nasal flux by 56% relative to free curcumin. Endothelial transport increased 1.57-fold without a significant change in transendothelial electrical resistance. In SK-N-SH cells, IC50 decreased from 78.94 to 69.67 µM at 24 h and from 70.54 to 50.24 µM at 48 h. Similar enhancement was observed in SH-SY5Y cells. Uptake was predominantly clathrin-dependent, accompanied by S-phase accumulation and reduced cell migration.Conclusions OptCUR-NS improved curcumin permeation, endothelial transport, cellular uptake, and in vitro anti-neuroblastoma activity while maintaining fibroblast cytocompatibility and endothelial monolayer integrity under the conditions tested.