# Redesigning the Viscosupplement to Enhance the Mechanical and Biological Actions of Hyaluronic Acid

> **NIH NIH R43** · PROHIBIX, LLC · 2021 · $250,300

## Abstract

Abstract
Knee osteoarthritis (OA) is an immobilizing chronic disease that drastically decreases quality of life. Intra-articular
injections of viscous, high molecular weight hyaluronic acid (HA) solutions are commonly administered to restore
viscoelastic properties of synovial fluid and reduce OA related joint pain. In addition to its mechanical effects,
cellular receptor binding to HA has been shown to reduce inflammatory signaling, cartilage degrading enzyme
activity, and stimulate endogenous production of HA. Despite the tremendous potential of HA in treating OA
based on its critical roles in joint function, sustaining high concentrations of exogenous HA in the synovial fluid
has been challenging and therefore its clinical efficacy limited. Traditional viscosupplements rely on the same
formulation approach of creating a viscous solution of HA, then introducing crosslinks to stabilize and retain HA
after injection. This approach and considerations of material viscosity and acceptable injection forces has limited
HA doses to less than 100 mg and half-lives to less than one week. In order to increase the dose and enhance
duration of HA treatment, Prohibix LLC has redesigned the HA viscosupplement into dense hydrogel
microparticles that slowly release high molecular weight HA into the synovial fluid over time. Our promising
preliminary results demonstrate the ability to deliver over 200 mg of HA in a single injection that releases HA for
over 4 weeks. This innovative HYALEASE hydrogel microparticle technology has tremendous potential to
improve the therapeutic efficacy of HA in treating OA, and also has great potential as a platform to encapsulate
and sustain the release of other promising but hard to formulate therapeutics. The objective of this Phase I SBIR
proposal is to continue the development of the HYALEASE microparticle technology including (i) demonstrate
biological activity of released HA, (ii) quantify synovial half-life in rats, and (iii) compare therapeutic efficacy to a
traditional viscosupplement using an industry adopted rat OA model. Completion of these Aims will further
motivate product development in a large animal model of OA (Phase II studies) towards first-in-man studies.

## Key facts

- **NIH application ID:** 10384520
- **Project number:** 1R43AR079965-01A1
- **Recipient organization:** PROHIBIX, LLC
- **Principal Investigator:** Brendan Purcell
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $250,300
- **Award type:** 1
- **Project period:** 2021-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384520

## Citation

> US National Institutes of Health, RePORTER application 10384520, Redesigning the Viscosupplement to Enhance the Mechanical and Biological Actions of Hyaluronic Acid (1R43AR079965-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10384520. Licensed CC0.

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