# Bioerodible corticosteroid microparticle-drug as an intra-articular drug delivery system for osteoarthritis therapy

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $146,599

## Abstract

Abstract
Osteoarthritis (OA) is one of the world’s leading causes of disability. About ~27 million adults in the U.S. have
symptomatic OA and suffer from chronic pain for several decades. Current clinical management of OA is
entirely palliative, and the definitive end-stage management is total joint arthroplasty. Consequently, there
exists an immediate and critical need to develop novel treatments that improve chronic pain and disability in
OA. Intra-articular corticosteroids have shown benefit over placebo in OA across all ages due to their ability to
reduce pain and mitigate joint inflammation. However, their efficacy is short-lived and is associated with dose-
dependent deleterious effects. We recently reported that therapeutic microparticles with the active drug
comprising near 100% of the particle’s matrix, i.e., no exogenous polymer, can be achieved via a gold-
nanoparticle templating method. Using this approach, this proposal seeks to develop corticosteroid-derived
microparticles for the intra-articular treatment of OA. We hypothesize that erodible particles that consist
almost entirely of the active drug molecules (>90%) will offer a controlled release of corticosteroids locally in
the diseased joint for an extended period, effectively reducing the pain and inflammation in OA while avoiding
adverse side effects associated with high doses, multiple treatments, and the use of exogenous biodegradable
polymers. Specifically, we will explore the fabrication of methylprednisolone succinate sodium salt (MPS)
particles by modifying our novel metal-nanoparticle templating method, which we have demonstrated for
generating composite bile salt particle that enables fine-tuned, controlled release of therapeutically active bile
salt. We will first mechanistically uncover how the fabrication parameters affect MPS-drug particle formation,
geometry, and erosion characteristics while also confirming long-term intra-articular retention (Aim 1). We will
then evaluate the anti-inflammatory capacity of the generated corticosteroid microparticles in vitro using OA-
relevant cell types, assessing modulation of inflammatory gene and protein expression. We will confirm that
corticosteroid particles have minimal deleterious effects on chondrocyte viability, proliferation, and extracellular
matrix maintenance (Aim 2.1). We will then evaluate the therapeutic efficacy of the novel corticosteroid
microparticles to control inflammation and pain in vivo using a clinically relevant mouse model of joint injury-
induced OA (Aim 2.2). Overall, the proposed work, if successful, can make transformative progress towards
the clinical treatment of OA and other joint disorders by providing a more efficacious and longer-lasting intra-
articular analgesic therapy.

## Key facts

- **NIH application ID:** 10465313
- **Project number:** 1R21AR080502-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Omolola Eniola-Adefeso
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $146,599
- **Award type:** 1
- **Project period:** 2022-09-23 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465313

## Citation

> US National Institutes of Health, RePORTER application 10465313, Bioerodible corticosteroid microparticle-drug as an intra-articular drug delivery system for osteoarthritis therapy (1R21AR080502-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10465313. Licensed CC0.

---

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