A microencapsulation strategy for intranasal semaglutide delivery

Semaglutide is a widely used treatment for weight loss, conventionally administered by subcutaneous injection. A non-invasive alternative is nasal delivery, which may improve ease of use and patient compliance. This study investigates the spray-drying microencapsulation of semaglutide using water-soluble polymers of varying molecular weights, including polyvinylpyrrolidone (PVP), combined with trehalose as a stabilising sugar. The process achieved over 90% semaglutide retention after three months of storage at 4 °C and encapsulation efficiencies exceeding 95% at a semaglutide concentration of 0.5 mg/mL, using a 1:1 sugar-to-polymer ratio. The resulting formulations fully dissolved in nasal mucus within two hours, with over 30% absorption occurring in the first 20 minutes. Toxicological testing showed no adverse effects on nasal cell lines. Enhanced transport across nasal cells was observed with higher trehalose content, achieving complete transport within two hours.