The Polymer Society of Korea

Abstract

Oral delivery of peptides, proteins, and nucleic acid therapeutics remains challenging due to enzymatic degradation and poor intestinal permeability. To overcome these barriers, we developed lipid-polymer hybrid nanoparticles with a layer-by-layer polymer coating for enhanced gastrointestinal stability and intestinal absorption. The multilayered polymer shell protects biomacromolecules from enzymatic degradation, while bile acid-functionalized chondroitin sulfate enables apical sodium-dependent bile acid transporter (ASBT)-mediated uptake in ileal enterocytes. Following internalization, the nanoparticles are incorporated into chylomicrons and transported via the intestinal lymphatic system, bypassing hepatic first-pass metabolism. This platform combines advanced polymeric architectures with transporter-mediated absorption and lymphatic routing to enhance the oral bioavailability of biopharmaceuticals.