How Peptide-Based Eyedrops Can Reach the Back of the Eye to Treat Serious Eye Diseases | Research

The takeaway

Cell-penetrating peptides, homing peptides, and supramolecular peptide-based eyedrops show promise for delivering drugs to the back of the eye through different routes, potentially replacing invasive eye injections.

Zero approved eyedrops
No topical eyedrop formulation has ever been clinically approved for treating diseases at the back of the eye, highlighting both the difficulty of the challenge and the enormous unmet medical need that peptide-based technologies aim to address.

What the researchers found

The review identifies three main routes by which topical eyedrops can reach the posterior segment of the eye: the corneal route, the conjunctival-vasculature route, and the conjunctival-scleral route. Different peptide-based technologies favor different pathways:

- Cell-penetrating homing peptides and lipid nanoparticle-encapsulated eyedrops primarily use the corneal route

- Cell-penetrating peptides and PepT-1-targeting ligands mainly use the conjunctival route

- Supramolecular peptide-based eyedrops, chitosan nanoparticles, and polymeric micelles can access the posterior segment through both routes

No topical eyedrop formulation has yet been clinically approved for treating ocular fundus (back-of-eye) diseases.

Why it matters

Millions of people with conditions like age-related macular degeneration and diabetic retinopathy currently rely on regular eye injections (intravitreal injections) that are painful, invasive, and require clinical visits. If peptide-based eyedrops can effectively deliver drugs to the back of the eye, it would be a transformative improvement in quality of life for these patients. This review maps the landscape of current approaches and their mechanisms.

How the study worked

This is a narrative review article that systematically summarizes recent advances in topical eyedrop therapies for posterior segment eye diseases. The authors categorized delivery technologies by their routes of access (corneal vs. conjunctival) and examined the mechanisms by which each formulation type crosses ocular barriers.

What this study cannot tell us

As a review article, this paper synthesizes existing research rather than presenting new experimental data. No eyedrop formulation for posterior segment diseases has reached clinical approval yet, so all approaches discussed remain experimental. The translation from preclinical models to human use is a major hurdle that many of these technologies have not yet cleared. Long-term safety data for most peptide-based formulations are limited.

How to read the evidence

This is a narrative review summarizing preclinical research and early-stage technologies. It provides a useful overview of the field but does not present new experimental data or follow systematic review methodology. The technologies discussed are largely pre-clinical.

When this study was published

Published in 2025, this is a very recent review that captures the latest advances in peptide-based ocular drug delivery, making it a current snapshot of this rapidly evolving field.

The bigger picture

The quest to deliver drugs to the back of the eye via simple eyedrops is one of the most active areas in ophthalmic drug delivery. Peptides play a central role because they can be engineered to penetrate biological barriers, target specific tissues, and self-assemble into drug-carrying structures. Success in this field would disrupt the multi-billion-dollar market for intravitreal injections and dramatically improve patient compliance and outcomes.

Questions still open

Which peptide-based eyedrop technology is closest to clinical trial approval for treating posterior segment diseases?
Can supramolecular peptide eyedrops achieve drug concentrations at the retina comparable to intravitreal injections?
What are the long-term safety profiles of repeated use of cell-penetrating peptide eyedrops on corneal and conjunctival tissues?

Common questions

Why can't regular eyedrops treat diseases at the back of the eye?

Regular eyedrops face two major obstacles: they are rapidly washed away by tears (most of the dose drains within minutes), and the eye has multiple biological barriers — including the cornea, conjunctiva, and blood-retinal barrier — that prevent drugs from reaching the retina and other posterior structures. That's why current treatments for diseases like macular degeneration require direct injection into the eye.

How do peptide-based eyedrops work differently from regular eyedrops?

Peptide-based eyedrops use specially designed peptides that can penetrate the eye's barriers. Cell-penetrating peptides act like molecular keys that open pathways through corneal or conjunctival tissue. Homing peptides can target specific tissues in the eye. Supramolecular peptide formulations self-assemble into structures that can carry drugs through multiple routes simultaneously. These technologies aim to deliver therapeutic drug levels to the back of the eye using simple, non-invasive eyedrops.

Read the original research

Delivery Routes of Topical Eyedrops Reaching the Posterior Segment of the Eye-Recent Advances.

Chemistry (Weinheim an der Bergstrasse, Germany), 31(72), e02324

View on PubMed ↗Publisher’s paper ↗

Citation

Ye, Yuhong; Zhang, Ye; Zhao, Pan; Shen, Yaobang; Hu, Ping; Wang, Lei; Long, Da. (2025). Delivery Routes of Topical Eyedrops Reaching the Posterior Segment of the Eye-Recent Advances.. Chemistry (Weinheim an der Bergstrasse, Germany), 31(72), e02324. https://doi.org/10.1002/chem.202502324