Ceftriaxone-loaded albumin-based nanoparticles incorporated into in situ ionic sensitive nasal gels: Development, characterization, and nasal drug deposition studies.

Ceftriaxone (CFT) is recommended as the drug of choice for the empirical treatment of bacterial meningitis. However, conventional drug delivery has difficulty in crossing the blood-brain barrier (BBB), leading to insufficient therapeutic efficacy. Therefore, nasal drug administration emerged as a viable strategy, providing the opportunity for brain-targeted delivery to reach effective brain concentrations. In this work, we present the development of in situ nasal gels of CFT-loaded albumin nanoparticles for nose-to-brain delivery. The obtained formulations were characterized in terms of particle size, zeta potential, entrapment efficiency, expansion coefficient, droplet size distribution, in vitro drug release, permeability assay, nasal deposition studies, and antibacterial activities. The BBB-PAMPA permeability assay showed that the in situ nasal gels CFT formulation with 0.2% gellan gum (CFT-GG0.2%) has the highest permeation flux of all. Moreover, nasal deposition studies utilizing a 3D-printed human nasal cavity model revealed that CFT-GG0.2% was able to provide higher CFT concentration in the olfactory area. Interestingly, the developed in situ nasal gels formulation could successfully retain the antibacterial activities of CFT against S. agalactiae, H. influenzae, and N. meningitidis. Altogether, the in situ nasal gels formulation has the potential as a suitable delivery platform for CFT administration through the nose-to-brain delivery pathway.