Single intra‐articular injection of fluvastatin‐PLGA microspheres reduces cartilage degradation in rabbits with experimental osteoarthritis

Abstract

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.

Chitosan temperature-sensitive gels: reduce the burst release of microspheres containing lornoxicam and enhance drug targeting

“…9 PLGA microspheres have been proved to have good therapeutic effect in the treatment of osteoarthritis. [10][11][12] For instance, the SFN-PLGA microspheres system devised in this study that can be used for treating osteoarthritis, which indicates that SFN-PLGA microspheres delayed the progression of surgically-induced osteoarthritis in rats. 13 The intraarticular delivery of Lnxc loaded chitosan microspheres can minimize associated side-effect after prolonged oral administration.…”

Attenuation of osteoarthritis progression in mice following intra‐articular administration of simvastatin‐conjugated gelatin hydrogel

“…They found that there was a reduction in cartilage degradation that was possibly due to reduced production of cartilage‐degrading enzymes in the synovium; however, there was no significant effect on enzymes in the cartilage. Another study by the same group showed that fluvastatin‐loaded polylactic‐ co ‐glycolic acid microspheres reduced OA progression in a rabbit ACLT model (Goto et al, ). In that study, they also compared differences among simvastatin, fluvastatin, and rosuvastatin regarding their effects on some key gene expression changes in OA progression in vitro.…”

“…Previous in vitro studies have shown that statins protect chondrocytes by suppressing the expression of catabolic genes and stimulating the expression of anabolic genes (Dombrecht et al, ; Lazzerini et al, ; Simopoulou, Malizos, Poultsides, & Tsezou, ). The ability of statins to prevent the progression of OA has been proven in several animal models (Akasaki et al, ; Aktas, Sener, & Gocun, ; Bayyurt et al, ; Goto et al, ; Yudoh & Karasawa, ). Because statins are widely used in clinical practice, it is suggested that statins could be promising candidates for new OA drugs.…”

Urine Proteomics Profiling and Functional Characterization of Knee Osteoarthritis Using iTRAQ Technology

“…However, the exact mechanism of adiponectin and BBOX1 in the pathophysiology of OA still remains unknown. Further research is needed before lipid-lowering agents, such as fluvastatin, to be used as a therapy for OA [21].…”