# Systemic anti-inflammatory therapy to prevent or delay diabetic cataracts and treat post-surgical inflammation

> **NIH NIH R01** · UNIVERSITY OF ALABAMA IN TUSCALOOSA · 2021 · $360,163

## Abstract

PROJECT SUMMARY
 Currently, surgical intervention is the only cure for cataracts, though this can be complicated in patients
with diabetes. One of the most common postoperative complications in patients suffering from diabetes is
persistent inflammation (uveitis) that can cause significant corneal edema, posterior synechia, and progression
of diabetic retinopathy or neovascular glaucoma. There is substantial evidence that secondary cataract formation
due to health conditions such as diabetes are associated with increased inflammation, oxidative stress, and
sorbitol accumulation, along with covalent bonding of a protein or lipid molecule with a sugar molecule causing
an increase in advanced glycosylation end products (AGE) formation that can cause significant damage to cells
and tissues. The efforts to combat these effects using traditional drugs often leads to severe side effects
outweighing the benefits. On the other hand natural compounds such as curcumin offer promise, but their
progress is hampered due to lack of suitable dosage forms and poor bioavailability. In order to overcome inferior
physicochemical and pharmacological attributes of curcumin we have prepared biodegradable nanosystems of
polylactide-co-glycolide (PLGA) encapsulating curcumin (nCUR). These passively absorbed nCUR when given
8 mg/kg/day were significantly more effective than plain curcumin in delaying diabetic cataract in rodents,
independent of glucose reduction. Despite the enhanced performance of passive nCUR, a significant dose
remained unabsorbed in the intestine, indicating potential for further improvement through active-nanosystems.
For the first time, we present a non-competitive active transport strategy to improve drug transport across
biological barriers by developing carrier systems that have no equivalent in the world of competitive ligands. We
hypothesize that transferrin receptor (TfR) mediated delivery across the intestinal barriers (IB) and blood ocular
barriers (BOB) would significantly enhance the transport of the nanosystems making systemic anti-inflammatory
therapy a reality.
 In this proposal, we will continue our studies on non-competitive active drug delivery strategy and
understand how the systemic anti-inflammatory therapy will prevent or delay diabetic cataracts and manage
post-surgical inflammation. To test this hypothesis, we propose the following specific aims: AIM #1. Establish
the effectiveness of TfR in facilitating the transport of PLGA-GA NS across the IB and BOB in rat model. AIM #2.
Establish the magnitude of desired or undesired effects in suitable rat models as a result of active transport. AIM
#3. We will verify performance of this delivery strategy in a more man-like model. At the end of this study, we will
have an effective systemic anti-inflammatory therapy to prevent or delay diabetic cataracts and treat post-
surgical inflammation.

## Key facts

- **NIH application ID:** 10246426
- **Project number:** 5R01EY028169-06
- **Recipient organization:** UNIVERSITY OF ALABAMA IN TUSCALOOSA
- **Principal Investigator:** Ravikumar N Majeti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $360,163
- **Award type:** 5
- **Project period:** 2017-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246426

## Citation

> US National Institutes of Health, RePORTER application 10246426, Systemic anti-inflammatory therapy to prevent or delay diabetic cataracts and treat post-surgical inflammation (5R01EY028169-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246426. Licensed CC0.

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