# New method to treat or prevent corneal graft rejection

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $397,688

## Abstract

PROJECT SUMMARY
Corneal transplantation is the most common solid organ transplantation worldwide, and immunological graft
rejection is the main cause of graft failure. Corticosteroid eye drops must be applied frequently to prevent graft
rejection and rescue grafts that show early signs of rejection, because topically administered drugs undergo
rapid clearance and have poor ocular bioavailability. However, long-term, frequent dosing is associated with
low patient compliance, and those that comply have risk of increased intraocular pressure (IOP), which can
cause glaucoma. We propose a new method for providing sustained corticosteroid delivery at low, but
efficacious levels, removing the treatment burden from patients and improving the safety of corticosteroids. We
developed biodegradable nanoparticles containing high loadings of dexamethasone sodium phosphate (DSP)
that can be administered by the same route that surgeons administer DSP at the end of corneal transplant
surgery, subconjunctival (SCT) injection. Further, DSP-loaded nanoparticles (DSP-NP) are coated with
polyethylene glycol (PEG) to minimize inflammatory reactions in the eye, and in contrast to topical drops, do
not cause an increase in IOP in animal models. Our preliminary results demonstrate that DSP-NP are effective
for both preventing and treating early signs of graft rejection in a rat model. Here, our aim is to develop longer-
lasting formulations that can safely and effectively prevent and treat corneal graft rejection, for as long as 3
months with a single injection. If successful, this approach would significantly improve corneal transplant
patient care and prognosis. In Aim 1, we will confirm batch reproducibility, determine the maximum tolerated
dose (MTD), and assess ocular pharmacokinetics (PK). The two lead formulations will then be tested for dose
dependent efficacy for prevention and treatment in our rat model of graft rejection in Aim 2. Finally, we will
carry out detailed safety and pharmacokinetics studies of at least one lead DSP-NP formulation in rabbits in
Aim 3 to facilitate future development and potential clinical translation.

## Key facts

- **NIH application ID:** 9942455
- **Project number:** 5R01EY027827-04
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** QINGGUO XU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,688
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942455

## Citation

> US National Institutes of Health, RePORTER application 9942455, New method to treat or prevent corneal graft rejection (5R01EY027827-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9942455. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*