Synovial Macrophage Targeting Immunomodulatory Therapies for Post-Traumatic Osteoarthritis
Abstract
The primary hypothesis of the project is that direct delivery into the joints of a Folate Receptor-2 (FR-2) targeting drug carrier loaded withzoledronate (ZA), a bisphosphonate (BP) can selectively eliminate a subset of activated synovial macrophages, modulate joint inflammation, and modify disease outcomes of PTOA. The objectives of this project will be realized by two specific aims: Aim 1: Develop and evaluate folic acid functionalized microparticle for targeted and sustained delivery of bisphosphonate to FR-2+ activated macrophages. The goal of aim 1 is to develop polymer microparticle drug carrier which will selectively target activated macrophages expressing FR-2. The influence of selective removal of activated macrophages will be assessed by comparing inflammation state of the macrophages pre- and post- treatment. Aim 2: Detect presence of activated macrophages and evaluate therapeutic efficacy of macrophage targeting microparticles in a non-surgical, cyclical loading, clinically relevant mouse model of PTOA. ACL rupture will be induced in mice by cyclic mechanical loading of the knee joint. Similar to humans, this mouse model shows signs of rapid PTOA development following ACL rupture. Therapeutic benefits of the targeted drug carrier developed inAim1 in the mouse model will be determined by comparing disease outcomes and joint health between control (saline treated) and targeted drug carrier treated groups.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2022
- Accession Number
- AD1201007
Entities
People
- Era Jain
Organizations
- Syracuse University