Development of a nasal spray based on cyclodextrin/hydrophobically-modified hydroxypropyl-methyl cellulose for the prevention of viral respiratory infections

The work aims to develop mucoadhesive and thermo-responsive in situ gelling systems, using hydrophobically-modified hydroxypropyl-methyl cellulose (Sangelose, SG) and beta-cyclodextrin (β-CD) derivatives, for preventing viral respiratory infections. Eight SG/CD systems with varying CD concentrations were evaluated for rheological properties, mucoadhesiveness, spreadability and sprayability via nasal devices; cytotoxicity was in vitro investigated on reconstituted nasal epithelia. Additionally, droplet size distribution and spray deposition were assessed for the most promising systems. The addition of β-CD derivatives to SG solution was responsible for a rapid sol-gel transition within a physiological temperature range (29-34 °C). SG/CD systems were characterized by a prevalence of the elastic properties on the viscous ones at 37 °C, functional to the formation of a protective gel barrier on the mucosa. The most promising systems showed sprayability and spreadability suitable for nasal administration, while in vitro tests demonstrated their non-toxicity. All the sprays were characterized by droplets with size >100 μm, functional to avoid droplet exhalation or lung deposition; spray deposition studies confirmed uniform distribution across nasal turbinates, crucial for trapping inhaled particles. In conclusion, a mucoadhesive and thermo-responsive in situ gelling system consisting of SG and β-CD derivatives was successfully developed as promising nasal spray for the prevention of respiratory infections.