Evaluation of Citicoline-loaded Lutrol 127/Carbopol/Hyaluronic acid-based gels for brain delivery by intranasal administration.

The aim of this work was to evaluate two nasal gels specifically designed to meet three essential criteria: a suitable formulation for nasal administration, a pH compatible with the nasal mucosa, and the encapsulation capacity of the antioxidant Citicoline (CIT), which showed beneficial effects in neurological disorders such as Parkinson's disease. Hence, Carbopol 1342 (Carb) at different weights (5 mg or 25 mg), PF-127 and Hyaluronic acid (HA) provided two gelled systems, denoted as PF-127/Carb-5-HA" and "PF-127/Carb-25-HA", respectively. Gel mechanical and microstructural characterization was conducted using rheological tests and SEM observations. Moreover, in vitro CIT release in simulated nasal fluid showed a consistent burst effect for both gels. Ex vivo permeation studies using excised porcine nasal mucosa mounted on Franz cells confirmed that limited extent of CIT permeated from both formulations (7.8-9.5%). Interestingly, none of the gels was cytotoxic against the primary nasal epithelial cells (pNEC) and also when pNEC were co-cultured with the neuronal SH-SY5Y cells in order to provide an in vitro model of nose-brain axis (NBA). Finally, by SIRT1 quantification in the NBA model, the gels evidenced an effective neuronal inflammatory modulation, so being promising for nerve cell protection.