Marco Sorbona1 James Armstrong1 Mattias Björnmalm1 Molly Stevens1

1, Imperial College London, London, , United Kingdom

Osteoarthritis (OA) is a pathological condition that affects millions of people around the world, including approximately 30 million people in the US. OA is characterized by the deterioration of articular cartilage, preventing normal motion of the joint, which causes stiffness and pain. There are many promising therapeutic candidates for treating OA, however clinical outcomes are restricted by rapid clearance of the injected drug from the synovial fluid. Accordingly, the sustained and controlled release of therapeutics to the affected joints has become a major goal. The aim of this project is to develop an intra-articular injectable drug delivery system that promotes a sustained, triggered release of the OA therapeutic. The drug delivery system we developed is based on a core-shell structure where a polydopamine shell is assembled around a calcium carbonate template. This particulate system has several advantages for delivering OA therapeutics: 1) microscale dimensions enables improved retention in the synovial fluid without restricting movement (compared to smaller or larger delivery systems), 2) the polydopamine-based surface promotes adhesion (and hence retention) to the target tissue upon local administration, and 3) high drug loading capacity. The particles were synthesized and characterized using electron microscopy, flow cytometry and microelectrophoresis for zeta potential determination. The release profile of corticosteroid from the drug-loaded particles showed a prolonged release over a period of weeks. The adhesive properties of the polydopamine shells were tested by incubating the particles with cartilage explants: confocal fluorescence microscopy revealed the binding capacity of the particles to the cartilage surface. In conclusion, we demonstrate the assembly of a polydopamine-based drug delivery system which can deliver sustained quantities of corticosteroids in a spatio-temporal fashion. Ongoing and future work includes atomic force microscopy to further quantify the particle-cartilage interaction, co-culturing of particles with synovial cells (e.g. mesenchymal stem cells and synovial macrophages) to study their cytotoxicity and the effect of long-lasting drug release in vitro and in vivo work using osteoarthritic mouse model.