Abstract
A local sustained-release drug delivery system, or depot, for intra-articular injection offers the opportunity to release a therapeutic agent directly to the joint with limited need for reinjection. A successful system would provide more consistent efficacy and minimize systemic side effects. In this paper, we explore the potential use of diclofenac, a non-steroidal anti-inflammatory drug, for use in a polymer-conjugate depot system. During the course of our exploration it was determined that "conventional ester" conjugates of diclofenac were not appropriate as upon incubation in buffer (pH 7.4) or in bovine synovial fluid, a considerable amount of undesired diclofenac-lactam was released. Thus we developed a novel linker system for diclofenac in order to minimize the production of the lactam. This new linker enables a diclofenac conjugate system with tunable release rates and minimizes the production of undesired lactam side-products.
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