OBJECTIVE  To prepare liraglutide nasal thermosensitive in situ gel(Lrg-TS-ISG) which aims at altering the form of drug delivery from subcutaneous injection for nasal administration to enhance patient compliance and improve pharmacodynamics.

METHODS Using gelation temperature as the primary criterion, the proportions of thermosensitive gel matrices were screened via single-factor analysis. The formulation was optimized via central composite design (CCD) response surface methodology. The quality, stability, and in vitro release of Lrg-TS-ISG were evaluated. A type 2 diabetes model was established in SD rats, with subcutaneous liraglutide solution as the positive control and nasal saline as the negative control. Blood glucose reduction percentages post-administration were measured, and relative bioavailability was calculated. Nasal retention and fluorescence intensity were assessed through murine nasal imaging.

RESULTS The optimal formulation for the preparation of Lrg-TS-ISG: dissolving the prescribed amounts of P407, P188, PVP in PBS solution to 10 mL, swelling at 4 °C, then adding benzalkonium chloride and liraglutide, followed by uniform dispersion. Both the dissolution and release profiles of Lrg-TS-ISG followed zero-order kinetics. Pharmacodynamic data indicated higher bioavailability of Lrg-TS-ISG compared to liraglutide solution. Nasal fluorescence demonstrated that gel delivery could enhance nasal retention of liraglutide.

CONCLUSION  Lrg-TS-ISG exhibites a simple preparation process, prolonges nasal retention, and superior bioavailability versus subcutaneous injection. Nasal delivery improves patient compliance, offering a novel approach for non-invasive peptide administration.