Document Type
Poster
Date
4-10-2025
Keywords
Osteoarthritis therapy, Joint injury and pain, Veterans and military, Macrophages, Bisphosphonates drug, Drug delivery
Department
Biomedical and Chemical Engineering
Campus Community
BioInspired Institute
Language
English
Funder(s)
This work is supported by DoD Discovery Award, CUSE funds, and the Bernard D. and Louise C. Rostker Dissertation Fellowship Award by D'Aniello Institute for Veterans and Military Families (IVMF) at Syracuse University.
Funding ID
DoD Discovery Award: W81XWH2210020; CUSE grant: II-17-2020
Acknowledgements
We are thankful to the flow-cytometer core facility and Blatt Imaging center at Syracuse University and the Upstate TEM Core for their support in collecting the respective data presented in the manuscript.
Disciplines
Military and Veterans Studies
Description/Abstract
Post-traumatic osteoarthritis (PTOA) is a painful and debilitating disease that emerges following a joint injury. Given the rigorous nature of military training and the subsequent injuries sustained during service, the incidence of PTOA in military demographic is five-times higher than the general population, making it the leading medical cause of disability and early discharge from active duty. Emerging evidence suggests inflammatory macrophages as key drivers of PTOA progression, thus abating their activity may advance therapy. Zoledronate (Zol), a bisphosphonate with high macrophage-affinity and anti-inflammatory properties, has potential for PTOA treatment but is limited by low bioavailability, rapid joint-clearance and elevated cytotoxicity. To overcome these challenges, we developed a pH-responsive nanoparticle-in-microparticle (NiM) system (~7µm) for sustained Zol delivery to disease-driving macrophages. This system enables controlled drug-release over two weeks under physiological conditions ensuring minimal cytotoxicity. Notably, incorporating folic acid (FA) as a ligand to our system (NiM-FA) significantly enhanced uptake by RAW 264.7 macrophages, allowing us to modulate inflammation, reprogram macrophage phenotypes, and scavenge reactive oxygen species (ROS); all considered mediators of PTOA progression. In an ACL-ruptured non-surgical mouse model of PTOA, macrophages expressing folate-receptor β were detected in knee joints. Intra-articular administration of NiM-FA reduced pro-inflammatory macrophages and promoted a reparative phenotype. Encouraged by these immunomodulatory effects, ongoing studies are analyzing joint cartilage histology and assessing behavioral outcomes such as pain and gait in treated and injured mice groups. These findings highlight NiM-FA’s potential as a targeted therapy for PTOA, addressing a critical need for curative interventions in affected populations.
Recommended Citation
Sagoe, Paul; Zhang, Kaixiang; Zink, Benjamin; and Jain, Era, "Bisphosphonates Loaded Nanoparticles in Microparticles as Macrophage Targeting Immunomodulatory System for Post-Traumatic Osteoarthritis Therapy" (2025). Voices of Service Symposium. 23.
https://surface.syr.edu/vos/23
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Additional Information
This work is part of a larger volume of work involving the initial development and characterization of the drug delivery system used in this study. Publications to our previous work upon which this current study is based can be found at the links below: 1. https://doi.org/10.3390/molecules28186679 2. https://doi.org/10.1007/s13346-025-01889-7 3. https://apps.dtic.mil/sti/trecms/pdf/AD1201251.pdf