Enhanced inflammatory arthritis therapy with gallic acid-modified triamcinolone acetonide: A sucrose acetate isobutyrate-based sustained release depot

Abstract

Inflammatory arthritis primarily involves rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA), both characterized by shared inflammation in the articular joints and cartilage degeneration. These conditions lead to joint pain, loss of function, and a decline in quality of life. Triamcinolone acetonide (TA), an intermediate-acting synthetic glucocorticoid, is widely used as an anti-inflammatory agent for the treatment of inflammatory arthritis. However, its clinical application faces challenges such as rapid clearance from the joint cavity following intra-articular (IA) administration, the risk of joint damage with repeated injections, and the invasive nature of the IA injection route. To address these drawbacks, we propose sucrose acetate isobutyrate (SAIB), a biocompatible matrix, as a promising strategy for sustained drug release via intramuscular (IM) injection. Building on this approach, we designed a gallic acid-modified triamcinolone acetonide derivative (TA-GA) and incorporated it into the SAIB matrix to create the TA-GA-SAIB depot. The modification of TA with gallic acid (GA) effectively mitigates the burst release commonly observed in SAIB formulations, attributed to hydrogen bonding interactions between TA-GA and the SAIB matrix. Benzyl alcohol (BA) was selected as the optimal solvent to achieve minimal burst release during the in vitro drug release study. The TA-GA-SAIB depot exhibited sustained in vivo drug release, enhanced anti-inflammatory effects, and significant improvement in cartilage damage, along with excellent safety and biocompatibility. The synergy between the SAIB matrix and TA-GA not only enables sustained drug release but also improves therapeutic efficacy, making it a promising system for the treatment of inflammatory arthritis via intramuscular administration.