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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Advisor: Andrés J. García, Ph.D. (Georgia Institute of Technology)
Committee Members:
Julia Babensee, Ph.D. (Georgia Institute of Technology)
Marc Levenston, Ph.D. (Stanford University)
L. Andrew Lyon, Ph.D. (Georgia Institute of Technology)
Nael McCarty, Ph.D. (Emory University)
Niren Murthy, Ph.D. (Georgia Institute of Technology)
Osteoarthritis (OA) affects 26 million Americans, or approximately 14% of the adult population. The incidence of OA will dramatically increase in the next 20 years as the US grows older and the rate of obesity continues to increase. There are currently no clinical interventions that cure OA. Current biomaterial delivery systems exhibit several limitations. First, most drug-delivery particles are hydrophobic, which is not optimal for hydrophilic protein encapsulation. Second, hydrophobic particles, such as PLGA, could cause wear damage to the already-fragile OA cartilage structure. Additionally, these particles usually suffer from non-specific protein adsorption, which causes increased phagocytosis and can lead to increased inflammation. New therapies that increase the effectiveness of OA treatments or reverse OA disease progression will greatly decrease the economic costs and individual pain associated with this disease. The goal of this project was to develop a new drug-delivering nanoparticle to deliver anti-inflammatory proteins for treating OA. Our central hypothesis is that a controlled release/presentation system will more effectively deliver anti-inflammatory protein therapies to the OA joint.
We synthesized a block copolymer that self-assembles into injectable, sub-micron-scale particles and allows for an anti-inflammatory protein, IL-1ra, to be tethered to its surface for efficient protein delivery. The block copolymer incorporated an oligo-ethylene monomer for tissue compatibility and non-fouling behavior, a 4-nitrophenol group for efficient protein tethering, and an highly hydrophobic monomer for particle stability. In vitro culture experiments demonstrated that the engineered nanoparticles specifically target receptors in cells associated with inflammation. Delivery experiments to the rat knee demonstrated increased retention of the anti-inflammatory protein when tethered to the particle. This project provides a basis for the rational design and synthesis of new drug- and protein-delivering modular polymer particles that can deliver multi-faceted therapies to treat OA.
