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

Norio Goto, Ken Okazaki, Yukio Akasaki, Kohei Ishihara, Koji Murakami, Kiyoshi Koyano, Yasunori Ayukawa, Noriyuki Yasunami, Tomohiro Masuzaki, Yasuharu Nakashima

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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.

Original languageEnglish
Pages (from-to)2465-2475
Number of pages11
JournalJournal of Orthopaedic Research
Volume35
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

Fingerprint

fluvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Intra-Articular Injections
Microspheres
Osteoarthritis
Cartilage
Rabbits
Therapeutic Uses
Joints
Mevalonic Acid
Control Groups
Drug Delivery Systems
Chondrocytes
polylactic acid-polyglycolic acid copolymer
Knee
Oxidoreductases

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine

Cite this

Single intra-articular injection of fluvastatin-PLGA microspheres reduces cartilage degradation in rabbits with experimental osteoarthritis. / Goto, Norio; Okazaki, Ken; Akasaki, Yukio; Ishihara, Kohei; Murakami, Koji; Koyano, Kiyoshi; Ayukawa, Yasunori; Yasunami, Noriyuki; Masuzaki, Tomohiro; Nakashima, Yasuharu.

In: Journal of Orthopaedic Research, Vol. 35, No. 11, 01.11.2017, p. 2465-2475.

Research output: Contribution to journalArticle

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