Enzymatic absorption promoters could enable oral delivery of peptide drugs like semaglutide and insulin
Enzymatic absorption promoters (protease inhibitors, mucus-degrading enzymes, tight junction openers) could overcome GI barriers to enable oral delivery of peptide drugs, with emerging strategies showing promise for non-invasive administration.
Quick Facts
What This Study Found
Three categories of enzymatic promoters: protease inhibitors (prevent degradation), mucolytic enzymes (clear mucus barrier), tight junction openers (enable paracellular transport). Applicable to oral, nasal, pulmonary peptide delivery.
Key Numbers
How They Did This
Narrative review of enzymatic strategies for improving non-invasive peptide drug absorption.
Why This Research Matters
Most peptide drugs (insulin, GLP-1 agonists, growth hormones) require injection—limiting patient compliance and access. Enabling oral delivery would transform treatment for millions of patients with diabetes, obesity, and hormonal conditions.
The Bigger Picture
The holy grail of peptide drug delivery—effective oral administration—is getting closer through enzymatic absorption technology. Combined with peptide engineering and nanoformulation, these approaches could make injectable peptides obsolete.
What This Study Doesn't Tell Us
Review of emerging technology. Most strategies are preclinical. Safety of chronic mucosal permeability enhancement needs evaluation. Bioavailability often remains low.
Questions This Raises
- ?Which combination of absorption promoters achieves sufficient oral bioavailability?
- ?Are chronic mucosal permeability changes safe long-term?
- ?Could enzymatic promoters enable oral insulin with practical bioavailability?
Trust & Context
- Key Stat:
- From injection to pill Enzymatic absorption promoters could overcome the three main barriers to oral peptide delivery: enzyme degradation, mucus, and tight epithelial junctions
- Evidence Grade:
- Technology review of preclinical and emerging approaches. Promising but most strategies not yet clinically validated.
- Study Age:
- Published in 2025.
- Original Title:
- Enzymatic absorption promoters for non-invasive peptide delivery.
- Published In:
- Journal of controlled release : official journal of the Controlled Release Society, 382, 113675 (2025)
- Authors:
- Steiger, Marilena Bohley, Steinauer, Angela, Gao, Daniel, Cerrejon, David Klein, Krupke, Hanna, Heussi, Miguel, Merkl, Padryk, Klipp, Alexander, Burger, Michael, Martin-Olmos, Cristina, Leroux, Jean-Christophe
- Database ID:
- RPEP-13678
Evidence Hierarchy
Frequently Asked Questions
Why can't most peptide drugs be taken as pills?
Peptide drugs like insulin are proteins that get destroyed by stomach acid and digestive enzymes, blocked by intestinal mucus, and cannot cross the tight barriers between gut cells. Enzymatic absorption promoters address each of these problems to enable oral delivery.
Will we ever have truly effective oral insulin?
It is getting closer. This review catalogs new enzymatic strategies that protect peptides from digestion, clear mucus barriers, and open temporary pathways through gut walls. Combined with advances in peptide engineering, oral insulin with practical bioavailability may be achievable within the next decade.
Read More on RethinkPeptides
Related articles coming soon.
Cite This Study
https://rethinkpeptides.com/research/RPEP-13678APA
Steiger, Marilena Bohley; Steinauer, Angela; Gao, Daniel; Cerrejon, David Klein; Krupke, Hanna; Heussi, Miguel; Merkl, Padryk; Klipp, Alexander; Burger, Michael; Martin-Olmos, Cristina; Leroux, Jean-Christophe. (2025). Enzymatic absorption promoters for non-invasive peptide delivery.. Journal of controlled release : official journal of the Controlled Release Society, 382, 113675. https://doi.org/10.1016/j.jconrel.2025.113675
MLA
Steiger, Marilena Bohley, et al. "Enzymatic absorption promoters for non-invasive peptide delivery.." Journal of controlled release : official journal of the Controlled Release Society, 2025. https://doi.org/10.1016/j.jconrel.2025.113675
RethinkPeptides
RethinkPeptides Research Database. "Enzymatic absorption promoters for non-invasive peptide deli..." RPEP-13678. Retrieved from https://rethinkpeptides.com/research/steiger-2025-enzymatic-absorption-promoters-for
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.