Acid-Stable Peptide Hydrogel Delivers Insulin with pH-Triggered Intestinal Release
G(RADA)4 self-assembling peptide hydrogel resisted gastric acid and pepsin for 14 days while enabling pH-triggered release of sulfasalazine (<5% at pH 2, 70% at pH 7.2) and insulin (<10% at pH 2, 75% at pH 7.2).
Quick Facts
What This Study Found
G(RADA)4 hydrogel: 25.9 mg/L production, 70.6% recovery, 14-day acid/pepsin stability. Drug release: sulfasalazine <5% (pH 2), 70% (pH 7.2); insulin <10% (pH 2), 75% (pH 7.2) through pH-mediated nanofiber disassembly.
Key Numbers
How They Did This
Systematic screening of X(RADA)4 variants (X = G/S/A/M/Q/D/C/H), characterization by CD, TEM, cryo-SEM, rheology, stability testing in acid/pepsin, and drug release profiling at gastric and intestinal pH for sulfasalazine and insulin.
Why This Research Matters
Oral delivery of peptide drugs like insulin could eliminate injections for millions. A pH-responsive hydrogel that protects drugs in the stomach and releases them in the intestine solves a key barrier.
The Bigger Picture
Self-assembling peptide hydrogels that respond to pH represent a breakthrough platform for oral delivery of sensitive drugs, potentially including insulin and other peptide therapeutics.
What This Study Doesn't Tell Us
In vitro release studies in simulated GI fluids. In vivo bioavailability not assessed. Manufacturing scalability needs evaluation.
Questions This Raises
- ?Would G(RADA)4-encapsulated insulin achieve meaningful oral bioavailability in animals?
- ?Can the hydrogel protect other sensitive peptide drugs?
- ?How does the hydrogel perform in the complex real GI environment?
Trust & Context
- Key Stat:
- 75% intestinal release Insulin held at <10% release in stomach acid then released 75% in intestinal conditions through pH-triggered nanofiber disassembly
- Evidence Grade:
- Thorough formulation science study with systematic variant screening. In vitro only but compelling pH-responsive release data.
- Study Age:
- Published in 2025.
- Original Title:
- Drug delivery system based on the novel acidic self-assembling peptide hydrogels: Insights into N-terminal modulation, assembly mechanism, and applications.
- Published In:
- Colloids and surfaces. B, Biointerfaces, 261, 115451 (2026)
- Authors:
- Guo, Yang, Deng, Yang, Huang, Wei(3), Song, Liang, Jia, Pengxin, Gao, Cungang, Xu, Fei, Liu, Wenshuai, Nian, Rui
- Database ID:
- RPEP-15241
Evidence Hierarchy
Frequently Asked Questions
Could this enable insulin pills?
This peptide hydrogel protects insulin from stomach destruction and releases it in the intestine. It is one of the most promising approaches to oral insulin delivery, though in vivo absorption still needs to be proven.
How does pH-triggered release work?
The peptide nanofibers form a stable gel in stomach acid (pH 2) but disassemble when they reach the intestine (pH 7.2), releasing the trapped drug exactly where it needs to be absorbed.
Read More on RethinkPeptides
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Cite This Study
https://rethinkpeptides.com/research/RPEP-15241APA
Guo, Yang; Deng, Yang; Huang, Wei; Song, Liang; Jia, Pengxin; Gao, Cungang; Xu, Fei; Liu, Wenshuai; Nian, Rui. (2026). Drug delivery system based on the novel acidic self-assembling peptide hydrogels: Insights into N-terminal modulation, assembly mechanism, and applications.. Colloids and surfaces. B, Biointerfaces, 261, 115451. https://doi.org/10.1016/j.colsurfb.2026.115451
MLA
Guo, Yang, et al. "Drug delivery system based on the novel acidic self-assembling peptide hydrogels: Insights into N-terminal modulation, assembly mechanism, and applications.." Colloids and surfaces. B, 2026. https://doi.org/10.1016/j.colsurfb.2026.115451
RethinkPeptides
RethinkPeptides Research Database. "Drug delivery system based on the novel acidic self-assembli..." RPEP-15241. Retrieved from https://rethinkpeptides.com/research/guo-2026-drug-delivery-system-based
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.