Current drugs, targets, and drug delivery systems for the treatment of dyslipidemia
Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of the mevalonate pathway. The anti-inflammatory effect of statins has been reported in recent years. The present study investigated therapeutic effects of the local administration of statin in osteoarthritis (OA). We assessed clinically used statins and selected fluvastatin for further experimentation, as it showed potent anabolic and anti-catabolic effects on human OA chondrocytes. To achieve controlled intra-articular administration of statin, we developed an intra-articular injectable statin using poly(lactic-co-glycolic acid) (PLGA) as a drug delivery system (DDS). The release profile of the statin was evaluated in vitro. Finally, therapeutic effects of fluvastatin-loaded PLGA microspheres (FLU-PLGA) were tested in a rabbit OA model. Rabbit knees were divided into four subgroups: group 1-A, PLGA-treated group; group 1-B, PLGA contralateral saline control group; group 2-A, FLU-PLGA-treated group; and group 2-B, FLU-PLGA contralateral saline control group. Histological analysis 5 weeks after intra-articular injection revealed that OARSI scores were lower in group 2-A. No significant differences in OARSI scores were observed between groups 1-A, 1-B, and 2-B. This study indicates that a single intra-articular injection of fluvastatin-loaded PLGA microspheres could be a novel therapeutic approach for treating patients with OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2465-2475, 2017.