Self-Assembled BSA–Poloxamer Nano-Complexes Enable Rapid Intranasal Delivery of Naloxone: Mechanistic Insights, Enhanced Permeation, and Translational Potential

Present investigation reports bovine serum albumin–poloxamer188 nano-complexes (BSA–PLX NC) designed to improve trans-epithelial transport and enhance intranasal delivery of naloxone hydrochloride (NHCl) for quick opioid toxicity reversal. Current formulations face challenges in epithelial permeation, mucociliary clearance, and CNS uptake delay.

NHCl-loaded-BSA–PLX nano-complexes were developed through optimized desolvation–complexation method, with their physicochemical properties analyzed via DLS, zeta potential, FTIR, DSC, and TEM. Dissociation behavior was studied in buffers at pH 8.5, 6.4, and 7.4. In vitro and ex vivo permeation studies were conducted using vertical Franz diffusion cell with cellulose membranes and fresh goat nasal mucosa, respectively.

Nano-complexes demonstrated uniform nanoscale size (81.25 ± 1.65 nm), highly negative surface charge (− 40.85 ± 0.62 mV), and strong complexation efficiency (83.70 ± 0.60%). TEM confirmed spherical, monodisperse nanostructures facilitating mucosal interaction. Nano-complexes shows strong intermolecular stabilization at pH 8.5. Nasal pH causes partial protonation of BSA, weakening interactions, leading to structural relaxation and drug release. While, pH 7.4 causes rapid electrostatic screening, resulting in drug release within 30 min. In vitro diffusion study exhibited highest %drug release from nano-complexes, reaching 90 ± 2.45% at 60 min, versus 47.2 ± 1.3% for plain NHCl. Ex vivo permeation reached 87.1 ± 1.52% within 60 min, corresponding to 1.98-fold increase in apparent permeability (Papp = 3.78 × 10⁻⁴ cm/s) over plain drug.

NHCl–BSA–PLX NCs enhance nasal drug permeation, increase drug flux, and demonstrate potential for rapid CNS availability. Its self-assembled architecture and compatibility with scalable manufacturing position it as promising approach for intranasal emergency opioid reversal and broader CNS drug delivery applications.