Sublingual Semaglutide Nanofiber Film (InStrip) Attenuated Minipig Weight Gain More Than Oral Tablet

Patient adherence to chronic therapies for conditions like obesity and type 2 diabetes is often limited by conventional injectable or oral tablet formulations. While oromucosal delivery, particularly via oral thin films, offers improved convenience, existing production methods struggle to incorporate sensitive peptide drugs like semaglutide. This study addresses this gap by developing an electrospun nanofiber platform for sublingual semaglutide, aiming to enhance patient compliance and therapeutic efficacy.

Researchers developed semaglutide-loaded InStrips using electrospinning technology. Forty female, non-diabetic, non-obese Göttingen minipigs (6-7 months) were assigned to sublingual (InStrip), peroral (Rybelsus), subcutaneous (Ozempic), or placebo groups. Sublingual and peroral doses were administered thrice weekly, while subcutaneous was once weekly, over 8 weeks with a 1-week follow-up. Permeation enhancers, either sodium dodecyl sulphate (SDS) or sodium N-[8-(2-hydroxybenzoyl)amino] caprylate (SNAC), were incorporated into InStrip formulations. Primary endpoints included weight gain attenuation and biomarker responses.

Over 9 weeks, sublingual InStrip administration of semaglutide significantly attenuated weight gain by 24.9% compared to the placebo group. This effect surpassed that observed with the conventional oral tablet (Rybelsus) group. Growth trajectory analysis revealed a statistically significant difference between the sublingual InStrip and placebo groups (p=0.013). Beyond superior weight management, InStrip semaglutide also enhanced both insulin and C-peptide levels, indicating improved beta-cell function and glucose homeostasis. These biomarker improvements further support the enhanced systemic absorption and biological activity of semaglutide delivered via the nanofiber film.