Mathilde Sophie Felding1, Charlotte Cubbin1, Amalie Kjær Andresen1, Stine Rønholt2, Fatemeh Ajalloueian1 & Line Hagner Nielsen1
1Technical University of Denmark, Ørsteds Plads 345C, Kongens Lyngby, 2800, Denmark
2University of Copenhagen, Department of Pharmacy, Universitetsparken 2, Copenhagen, 2100, Denmark
Summary
Nasal administration of antibiotics possesses several advantages compared to conventional systemic administration as systemic administration of antibiotics is associated with adverse effects. However, the mucociliary clearance in the nasal cavity limits the residence time by providing a rapid clearance of the drug formulation. To overcome this challenge, an innovative intranasal formulation was developed using thermosensitive in situ hydrogels for delivering antibiotics to treat chronic rhinosinusitis. Thermosensitive in situ hydrogels are liquid at room temperature, enabling spraying of the formulation, but they transition into a gel when in contact with body temperature. This transition enables the formulation to retain in the nasal cavity. Characterisation of the thermosensitive in situ hydrogels is essential for further development. In this study, rheological characterization, drug release tests and cytotoxicity studies were conducted, followed by investigation of nasal deposition. Rheological studies showed that the sol-to-gel temperature and viscosity could be altered with the addition of hyaluronic acid to the thermosensitive hydrogels. Furthermore, drug release could be extended from 24 to 96 h with the addition of hyaluronic acid, and cytotoxicity studies revealed no cytotoxic behaviour towards nasal epithelial cells. The nasal deposition was evaluated in the Alberta Idealized Nasal Inlet (AINI) model, at 35°C, with a 30° angle of administration and a 15 L/min flow rate. Mucin coating was applied to simulate nasal mucosal conditions. The thermosensitive in situ hydrogels were able to deposit in high concentrations in the turbinates of the AINI, which is promising for local administration of antibiotics to the nasal sinuses.