Inhibition of the IL-1beta-induced Expression of Matrix Metalloproteinases by Controlled Release of IL-1 Receptor Antagonist Using Injectable and Thermo-reversible Gels in Human Osteoarthritis Chondrocytes.
- Author:
Jae Bum JUN
1
;
Jang Kyoung KIM
;
Tae Hwan KIM
;
Young In NA
;
Choong Hyeok CHOI
;
Yong Hee KIM
Author Information
- Publication Type:Original Article
- Keywords: Drug delivery system; Interleukin-1; Interleukin-1 receptor antagonist; Methylcellulose gel; Osteoarthritis
- MeSH: Arthritis; Cartilage; Cartilage, Articular; Chondrocytes; Drug Delivery Systems; Gels; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Joints; Knee; Matrix Metalloproteinases; Methylcellulose; Osteoarthritis; Real-Time Polymerase Chain Reaction
- From:Journal of Rheumatic Diseases 2011;18(2):85-93
- CountryRepublic of Korea
- Language:English
- Abstract: OBJECTIVE: IL-1beta is involved in the degradation of articular cartilage in various arthritides, including osteoarthritis (OA). Competitive inhibition of IL-1beta by IL-1 receptor antagonists (IL-1Ra) may represent a pathogenesis-based strategy for inhibiting degradation of the cartilage matrix. We investigated the hypothesis that controlled release of IL-1Ra using injectable, thermoreversible and complex coacervate combination gels as drug delivery systems might reduce matrix degradation in OA. METHODS: Thermoreversible combination gels that can be injected into joints were formed in aqueous solution by making a complex coacervate with recombinant human IL-1Ra (anakinra) and cationic macromolecules, and this was followed by co-formulation with methylcellulose as a negative thermosensitive polysaccharide. Gels containing anakinra were positioned in the upper insert of a transwell system and human OA chondrocytes were placed in the lower compartment and then they were stimulated with IL-1beta. The expression of matrix metalloproteinases (MMPs) was examined by performing real time PCR and ELISA. RESULTS: Complex coacervation between anakinra and protamine was successfully completed. IL-1Ra was released from the gels in a sustained release pattern for extended periods with minimal initial bursts. IL-1beta markedly enhanced the expression of MMP. The IL-1Ra released from the gels significantly inhibited the IL-1beta-induced MMP expression in the chondrocytes. CONCLUSION: We developed and optimized a novel injectable and thermoreversible gel system for the controlled release of IL-1Ra, and this drug delivery system effectively inhibited the IL-1beta-induced MMP expression of chondrocytes in a transwell system. Intra-articular local delivery of injectable and thermoreversible gels containing IL-1Ra into knees has the potential to provide prolonged therapy based on the pathophysiology of knee OA.
