Spider peptide segment enables intranasal delivery of GLP-1 and insulin with significant blood sugar reduction | Research

The takeaway

A 17-residue functional peptide segment (FPS) from spider egg toxin enhanced intranasal delivery of GLP-1 analogue and insulin in mice, with FPS-GLP showing significantly superior hypoglycemic effect versus unmodified GLP-1 and FPS-Ins matching intramuscular injection.

Nasal = injectable for insulin
Spider-derived peptide vector enabled intranasal insulin delivery matching intramuscular injection efficacy—potentially eliminating the need for needles

What the researchers found

FPS-GLP: concentration-dependent cell entry in vitro. Intranasal FPS-GLP > GLP-1 analogue alone for hypoglycemia. Intranasal FPS-Ins ≈ intramuscular FPS-Ins for blood sugar reduction. 17-residue C-terminal FPS as transmembrane delivery vector.

Why it matters

Injectable administration is the main barrier to peptide drug compliance. A spider-derived nasal delivery system could enable non-invasive delivery of GLP-1 drugs and insulin, dramatically improving patient convenience.

How the study worked

Solid phase synthesis (FPS-GLP), heterologous expression (FPS-Ins). A549 cell entry assays (Western blot). Mouse intranasal administration. Blood glucose monitoring.

What this study cannot tell us

Proof of concept only. Mouse study. Specific bioavailability numbers not stated. Long-term safety of repeated intranasal FPS use unknown. Scale-up challenges.

How to read the evidence

Proof-of-concept preclinical study. Demonstrates feasibility of the delivery approach.

When this study was published

Published in 2025.

The bigger picture

Spider venoms and toxins are proving to be rich sources of cell-penetrating peptides. Repurposing these for drug delivery is an innovative approach that combines evolutionary optimization with pharmaceutical need.

Questions still open

Could FPS enable nasal delivery of semaglutide specifically?
What is the FPS safety profile with repeated nasal administration?
Would FPS-modified peptides work for other CNS-targeted drugs?

Common questions

Could you take insulin as a nasal spray?

This study shows it may be possible using a spider-derived delivery peptide. When insulin was fused to a small cell-penetrating peptide from spider egg toxin and delivered through the nose, it lowered blood sugar as effectively as an injection. This could eventually replace needles for diabetic patients.

How does a spider peptide help with drug delivery?

The 17-amino acid peptide segment (FPS) from Latroeggtoxin-VI has evolved to penetrate cell membranes efficiently. When attached to drug peptides like GLP-1 or insulin, it carries them through the nasal membrane into the bloodstream, enabling non-injectable delivery.

Read the original research

Intranasal Absorption Enhancement of Antidiabetic Therapeuticals by the Functional Peptide Segment of Latroeggtoxin-VI.

Molecular pharmaceutics, 22(7), 4046-4055

View on PubMed ↗Publisher’s paper ↗

Citation

Sun, Minglu; Yin, Panfeng; Chen, Si; Wang, Xianchun. (2025). Intranasal Absorption Enhancement of Antidiabetic Therapeuticals by the Functional Peptide Segment of Latroeggtoxin-VI.. Molecular pharmaceutics, 22(7), 4046-4055. https://doi.org/10.1021/acs.molpharmaceut.5c00293