Permeation enhancer-induced membrane defects assist the oral absorption of peptide drugs.

ABSTRACT: The passive membrane permeation of small-molecule drugs and small hydrophobic peptides is relatively well understood. In contrast, how long polar peptides can pass through a membrane has remained a mystery. This process can be achieved with permeation enhancers, contributing significantly to the oral transcellular absorption of important peptide drugs like semaglutide - the active pharmaceutical ingredient in Ozempic, which is used as Rybelsus in a successful oral formulation. Here we now provide a detailed, plausible molecular mechanism of how such a polar peptide can realistically pass through a membrane paired with the permeation enhancer salcaprozate sodium (SNAC). We provide both simulation results, obtained with scalable continuous constant pH molecular dynamics (CpHMD) simulations,

SUBMITTER: Colston KJ 

PROVIDER: S-EPMC12568990 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature