Abstract
Intra-articular (IA) administration of therapeutic agents has been employed to selectively deliver active compounds at their site of action for the treatment of chronic joint diseases such as osteoarthritis, rheumatoid arthritis, and joint pain. Direct IA delivery of active compounds to local tissues occasionally provides improved therapeutic outcomes with reduced dose, while minimizing systemic exposure and undesirable adverse effects. However, many small drugs (< 10,000 Da) administered intra-articularly, tend to be rapidly effluxed from the synovium into the blood stream, thus requiring frequent IA injection. To date, different pharmaceutical approaches have been investigated, including polymer and/or lipid-based nanoparticles (NPs), microparticles (MPs), conventional and/or thermo-responsive hydrogels, drug suspension, and oily depot systems, to prolong the drug retention time in the joint, thus improving the pharmacokinetic profile and/or the therapeutic efficacy of active compounds. Herein, we have summarized the recent research trends on IA delivery systems with a focus on NPs, MPs, and hydrogel system, which have been studied most extensively to achieve extended retention time following IA injection.
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