An effective approach in osteoarthritis: Diacerein-loaded solid lipid nanoparticles, preparation and evaluation for targeted therapy

Abstract

Diacerein (DC) is primarily used for the treatment of degenerative diseases, such as osteoarthritis (OA). The purpose of this study is to develop a stable targeted preparation of DC for intra-articular delivery with prolonged effect. The Response Surface methodology approach was applied to optimize DC-loaded solid lipid nanoparticles (DC-SLNs). For optimization of SLNs, the DC-SLNs were fabricated with different ratios of stearic acid and glyceryl monostearate. SLNs of DC were prepared by a hot homogenization process and were characterized for particle size, zeta potential, polydispersity index, entrapment efficiency, and drug loading. FTIR, DSC, PXRD, and SEM analysis were also performed. In-vitro dissolution studies were also performed for 24 h. In-vivo studies were executed by utilizing papain-induced osteoarthritis rat model including plain DC and DC-SLNs administered orally and intra-articularly. The knee diameter was measured and behavioral studies were done which include the gait analysis, locomotor activity, and forced swim test. The results of these studies revealed that DC-SLNs administered intra-articularly have anti-inflammatory effects in the osteoarthritic rat model. Biochemical analysis displayed a positive effect on the osteoarthritic animal model. The inflammatory marker mediators like; TNF-α, IL-6, and NF-κB, were evaluated and indicated that intra-articular administration of DC-SLNs IA inhibited the inflammation and was also found effective in protecting against cartilage degradation. Thus, the study concluded that DC-SLNs IA can be used as an efficient anti-inflammatory delivery system with minimal side effects.