Tripterine and all-trans retinoic acid (ATRA)–loaded lipid-polymer hybrid nanoparticles for synergistic anti-arthritic therapy against inflammatory arthritis

Abstract

Arthritis of joints remains a hard-to-treat disease due to the low drug exposure to the articular cavity. Present study was intended to develop a Tripterine (TRI) and all-trans retinoic acid (ATRA)-loaded lipid-polymer hybrid nanoparticles (ATLP) for enhanced antiarthritic efficacy in arthritis conditions. We have showed that two drugs could be loaded with high loading capacity and control the release kinetics in a pH-responsive manner. The ATLP showed strong inhibitory effects on the expressions of TNF-α, IL-6 and IL-1β in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at the in vitro conditions. Compared to individual drugs (TRI and ATRA), ATLP significantly reduced the paw thickness exhibiting potent inhibition of inflammation. Consistently, ATLP resulted in lowest clinical score compared to that of individual drug indicating the remarkable improvement in the recession of inflammation. We have clearly demonstrated that the nanoparticulate based co-delivery of drugs could abolish the adverse effects of free drug as indicated by the body weight changes. Importantly, ATLP resulted in significant reduction of mRNA of TNF-α, IL-6, IFN-ϒ and IL-17 compared to either free drugs or CIA mice. Overall, ATLP represent a promising therapeutic strategy for the treatment of arthritis conditions.