Molecular targeting of FATP4 transporter for oral delivery of therapeutic peptide

Zhenhua Hu, Sara Nizzero, Shreya Goel, Louis E. Hinkle, Xiaoyan Wu, Chao Li, Mauro Ferrari, Haifa Shen

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Low oral bioavailability of peptide drugs has limited their application to parenteral administration, which suffers from poor patient compliance. Here, we show that molecular targeting of the FATP4 transporter is an effective approach to specifically transport long-chain fatty acid (LCFA)–conjugated peptides across the enterocytic membrane and, thus, enables oral delivery of drug peptides. We packaged LCFA-conjugated exendin-4 (LCFA-Ex4) into liposomes and coated with chitosan nanoparticles to form an orally deliverable Ex4 (OraEx4). OraEx4 protected LCFA-Ex4 from damage by the gastric fluid and released LCFA-Ex4 in the intestinal cavity, where LCFA-Ex4 was transported across the enterocyte membrane by the FAPT4 transporter. OraEx4 had a high bioavailability of 24.8% with respect to subcutaneous injection and exhibited a substantial hypoglycemic effect in murine models of diabetes mellitus. Thus, molecular targeting of the FATP4 transporter enhances oral absorption of therapeutic peptides and provides a platform for oral peptide drug development.

Original languageEnglish (US)
Article numbereaba0145
JournalScience advances
Volume6
Issue number14
DOIs
StatePublished - Apr 2020

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Molecular targeting of FATP4 transporter for oral delivery of therapeutic peptide'. Together they form a unique fingerprint.

Cite this