Transporter-Driven Supramolecular Nanocomplex for Oral Delivery of Peptide Therapeutics

Yeonsu Ryu – student, konkuk university; Bison Seo – student, konkuk university; Minho Seo – student, konkuk university; Jae-Hyeon Lee – student, konkuk university; Seong-Bin Yang – Post Dr, konkuk university; Jooho Park – professor, konkuk university

Introduction:

Glucagon-like peptide-1(GLP-1) receptor agonists have emerged as transformative therapeutics for obesity, diabetes, and metabolic dysfunction–associated steatohepatitis(MASH). However, peptide therapeutics such as semaglutide suffer from poor oral bioavailability and limited intestinal permeability. Current oral formulations rely on nonspecific absorption enhancers and strict dosing conditions. Transporter-mediated uptake pathways offer a more targeted and physiologically relevant strategy. Here, we developed a supramolecular nanocomplex that enables apical sodium-dependent bile acid transporter (ASBT)-mediated uptake to enhance the oral absorption of semaglutide.