Solvent exchange-motivated and tunable in situ forming implants sustaining triamcinolone acetonide release for arthritis treatment

Abstract

Arthritis is a syndrome characterized by inflammation in the joints. Triamcinolone acetonide (TA) was used as an anti-inflammatory agent in the treatment of this disease. However, there are limitations to its clinical application, including rapid clearance from the joint cavity, potential joint damage from multiple injections, and adverse joint events. To address these drawbacks, we developed a tunable in situ forming implant loaded with TA. This injectable polymer solution utilized poly (lactic-co-glycolic acid) (PLGA) as an extended-release material. When injected into the joints, the solution solidifies into implants through a solvent exchange in the aqueous environment. The implants demonstrated robust retention at the injection site and released TA over several weeks even months through diffusion and erosion. By adding different proportions of low water-miscible plasticizers, the release period of the drug could be precisely adjusted. The plasticizers-optimized implants exhibited a tough texture, enhancing the therapeutic efficiency and drug safety in vivo. In arthritic model studies, the tunable TA-loaded implants significantly reduced swelling, pain, and motor discoordination, and also showed suppression of arthritis progression to some extent. These findings suggested that TA-loaded ISFI holds promise for managing inflammatory disorders in individuals with arthritis.