# Nanogels for Drug Delivery across the BRB to Treat Diabetic Retinopathy

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $386,250

## Abstract

While new therapeutics, especially protein drugs such as Avastin, Lucentis and growth factors, are being
developed for treating retinal diseases, such as diabetic retinopathy and macular degeneration, the use of these
therapeutics is still hampered by the need for more effective method of delivery. The reason is that these
therapeutics have short half-lives, do not or hardly cross the blood retinal barrier (BRB), and can cause toxicity
and side effects at high dose. Nanoparticles show great promise for transporting drugs across biological barriers,
reducing drug clearance, and improving the bioavailability of drugs at targets. However, no nanoparticles have
been developed to effectively deliver drugs across the BRB yet. The long-range goal of this project is to develop
novel nanoparticles for long-term release of therapeutics across the BRB to treat retinal diseases. The immediate
objective is to develop unique subconjunctivally injectable, thermoresponsive and biodegradable nanogels for
aqueous loading, enhanced stability and BRB permeability, and sustained release of protein drugs to treat early
diabetic retinopathy. For this specific objective, we will use insulin as a model protein drug for the development
of the nanogel drug delivery platform because insulin is a survival factor for endothelial and neural cells, and
plays an important role in retinal function. The hypothesis of the proposal is that subconjunctivally injectable
nanogels with tailored balance of hydrophilicity, hydrophobicity, charge content and hydrolytic degradation
properties, can act as an effective local delivery system platform for sustained release of therapeutics such as
insulin across the BRB to protect retinal cells from apoptosis and improve vascular leakage in diabetes. Three
specific aims are: 1) in vitro optimization and characterization of nanogels for aqueous loading, enhanced
stability, and sustained release of insulin; 2) in vitro and ex vivo optimization and characterization of nanogels
for enhanced insulin permeability across the sclera and the BRB; and 3) in vitro bioeffect, and in vivo
pharmacokinetics and bioeffect evaluations of subconjunctivally injected insulin-loaded nanogels. The proposed
nanogels are physicochemically, biologically, clinically and collaboratively innovative, and will provide a novel
periocular drug delivery platform for enhancing drug permeability across the BRB and achieving long-term drug
bioavailability in the retina to treat diabetic retinopathy and other retinal diseases.

## Key facts

- **NIH application ID:** 10000203
- **Project number:** 5R01EY023853-06
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Tao L Lowe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000203

## Citation

> US National Institutes of Health, RePORTER application 10000203, Nanogels for Drug Delivery across the BRB to Treat Diabetic Retinopathy (5R01EY023853-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000203. Licensed CC0.

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