Electrospun Nanofiber Oral Thin Film Platform for Sublingual Peptide Delivery: A Promising Alternative to Conventional Semaglutide Formulations

Background Administration of drugs via the oromucosal route, especially using oral thin films, improves patient adherence compared to conventional oral and injectable methods. However, existing production techniques for oral thin films face considerable challenges in incorporating peptide and protein drugs. This study presents electrospun nanofiber‐based oral thin film as a viable platform for the sublingual delivery of semaglutide. This platform was tested in Göttingen minipigs, which showed a greater response to attenuation of weight gain. Methods Semaglutide‐loaded InStrips were produced using electrospinning technology. Forty female, non‐diabetic, non‐obese Göttingen minipigs (6–7 months) were divided into groups based on sublingual ( InStrip ), peroral (Rybelsus), or subcutaneous (Ozempic) administration of semaglutide over 8 weeks, followed by a 1‐week follow‐up. InStrip formulations incorporated either sodium dodecyl sulphate (SDS) or sodium N ‐[8‐(2‐hydroxybenzoyl)amino] caprylate (SNAC) as permeation enhancers. Sublingual and peroral dosing occurred thrice weekly, whereas subcutaneous administration occurred once weekly. Results Compared to the placebo group, in over 9 weeks, InStrip administration resulted in attenuation in weight gain by 24.9%, surpassing that of the oral tablet (Rybelsus) group. Growth trajectory analysis showed statistically significant differences between the sublingual (InStrip) and placebo group ( p = 0.013). In addition to superior weight management, InStrip semaglutide enhanced insulin and C‐peptide levels. Conclusion Sublingual delivery of semaglutide via InStrip enabled significant weight‐modulating effects and improved biomarker responses compared to the placebo group. Despite limitations of a small study group and short duration, this study provides a strong foundation for further evaluation of InStrip as a viable delivery platform for semaglutide administration.