# Sustained release of fenofibrate for the treatment of diabetic retinopathy

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $551,841

## Abstract

PROJECT SUMMARY
 Diabetic retinopathy (DR) is the most common cause of severe vision loss in the working-age
population in the world. However, clinical studies have shown that approximately 40% DR patients do not
adequately respond to anti-VEGF drugs. There is no drug treatment for those 40% DR patients. Furthermore,
repeated bolus injections of these anti-VEGF agents are associated with risks of injection-associated side
effects, and are a big burden to patients and the healthcare system. Fenofibrate, a peroxisome proliferator-
activated receptor-α (PPARα) agonist, is the first low-cost and safe oral drug for DR with clinically proven
efficacy against retinal neovascularization and diabetic macular edema in diabetic patients. However, oral
fenofibrate has a short half-life and poor retinal absorption. An ocular fenofibrate delivery is needed for the
treatment of DR. Intravitreal injection (IVT) of fenofibrate free drug demonstrated a short half-life of the drug in
the eye, and frequent IVT injections of fenofibrate are needed to sustain the effect. We propose a new drug
delivery strategy for providing sustained intraocular fenofibrate to target a non-VEGF, PPARα pathway and
reducing the treatment burden from DR patients. Recently, we developed small-sized 200nm biodegradable
nanoparticles containing 6% fenofibrate (Feno-NP) that demonstrated drug release for at least 8 weeks in the
eye following an IVT injection, and have no detectable ocular toxicities. Our preliminary results further
demonstrated that a single IVT injection of Feno-NP was effective on DR in the streptozotocin (STZ)-induced
T1D rat model for 8 weeks. Here, our aim is to develop and optimize new longer-lasting large-sized fenofibrate-
loaded microparticles (Feno-MP) that have higher drug loadings (≥20%) with dense PEG coating, and can
safely and effectively treat DR, for ≥ 6 months with a single IVT injection. If successful, this approach would
significantly improve DR patient care. In Aim 1, we will optimize and characterize reproducible large-sized
Feno-MP formulations that release fenofibrate for ≥6 months, determine the maximum tolerated dose, and
assess ocular pharmacokinetics (PK). The two most promising Feno-MP formulations will then be tested for
dose dependent efficacy on retinal vascular leakage and inflammation in STZ-induced diabetic rats (T1D
model) and db/db mice (T2D model) in Aim 2. Finally, we will carry out detailed safety and ocular PK studies of
one lead Feno-MP formulation in rabbits in Aim 3 to facilitate future development and potential clinical
translation.

## Key facts

- **NIH application ID:** 10521702
- **Project number:** 1R01EY033477-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Jian-Xing Jay Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $551,841
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10521702

## Citation

> US National Institutes of Health, RePORTER application 10521702, Sustained release of fenofibrate for the treatment of diabetic retinopathy (1R01EY033477-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10521702. Licensed CC0.

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