title: 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.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Goto
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okazaki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Akasaki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ishihara
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Section of Implant and Rehabilitative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Koyano
authors.affiliation: Section of Implant and Rehabilitative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ayukawa
authors.affiliation: Section of Implant and Rehabilitative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yasunami
authors.affiliation: Department of Oral Maxillofacial Prosthodontics, Field of Oral and Maxillofacial Rehabilitation, Advanced Therapeutic Course, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima, 890-8544, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Masuzaki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002358:Cartilage, Articular / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D019344:Lactic Acid; D008863:Microspheres; D010003:Osteoarthritis / Q000188:drug therapy*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D061251:Primary Cell Culture; D011817:Rabbits
chemical_list: D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077340:Fluvastatin
keywords: PLGA microspheres; fluvastatin; intra-articular injection; osteoarthritis; statin