# Collagen-mediated approaches to improve the local delivery and hypothermic release of osteoarthritis therapeutics

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2023 · $637,927

## Abstract

PROJECT SUMMARY
Post-traumatic osteoarthritis (PTOA) is an insidious consequence of joint injury, ~50% of patients with knee-
injuries exhibit PTOA within 10-years of injury. Presently, no cure for PTOA exists, but the acute nature of the
precipitating injuries provides for a unique approach to PTOA treatment: targeted prophylactic pharmaceutical
intervention to mitigate/prevent the initiation of disease post-injury. Many pre-clinical investigations for targeted
treatment have been conducted. However, due to incredibly rapid intra-articular (i.a.) drug clearance, disease-
modifying drug efficiency is highly limited, requiring repeated high-dose administration of free drug for efficacy.
Give the inefficiencies of i.a. administration of free drug, delivery approaches that extend drug-residence time
by targeting the tissues of the injured joint could represent a cost-effective method of increasing therapeutic
efficacy. We propose a novel and versatile platform for the thermally responsive, localized delivery of candidate
PTOA drugs to injured joints to limit initiation/progression of PTOA. Our approach relies on our pioneering
development of elastin-collagen-peptide conjugates that uniquely form cargo-laden nanovesicles that facilitate
long-term passive release at body temperature and accelerated-/burst-delivery at mildly hypothermic
temperatures. In addition, the collagen-like peptides comprising the vesicle’s outer ‘shell’ can target denatured
collagens, allowing accumulation in tissues with elevated collagen damage/remodeling.
In this proposal, we will evaluate the loading of candidate PTOA disease-modifying drugs (with a focus on
dexamethasone (Dex)) in refined elastin-collagen nano-vesicles (ECnV) and monitor their stability, as well as
passive and hypothermally-triggered drug release. Studies on naïve and ‘injured/activated’ chondrocytes,
synovial fibroblasts, and monocyte/macrophages, and articular cartilage and synovial tissue explants, will
confirm the cyto-/biocompatibility and quantify the suppression of ‘injury’ markers by Dex-loaded ECnVs. We
will conduct in vivo experiments using a non-invasive repeated joint loading (overuse) model of PTOA to
demonstrate the selective retention of ECnVs within injured joints after intra-articular (i.a.) injection. Multi-scale
in vivo, in situ, and histological/immunohistochemical analyses will be employed to evaluate the
pharmacokinetics of passively and hypothermally-triggered cargo release, tissue localization/biodistribution,
and the local and systemic biocompatibility/safety of ECnVs delivered to both healthy and early-PTOA joints.
Finally, we will characterize the ability of ECnV-based delivery of Dex to improve disease-modifying physiology
and PTOA outcomes prophylactically in the aforementioned non-invasive, joint injury model, with standard i.a.
liposomal and free-Dex treatments serving as comparators. Although the proposed work focuses on increasing
PTOA therapy effectiveness, it will also la...

## Key facts

- **NIH application ID:** 10595325
- **Project number:** 1R01AR080707-01A1
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Kristi L Kiick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $637,927
- **Award type:** 1
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595325

## Citation

> US National Institutes of Health, RePORTER application 10595325, Collagen-mediated approaches to improve the local delivery and hypothermic release of osteoarthritis therapeutics (1R01AR080707-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10595325. Licensed CC0.

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