Rhein laden pH-responsive polymeric nanoparticles for treatment of osteoarthritis
Bo Hu, Feng Gao, Chunbao Li, Boqing Zhang, Mingyang An, Ming Lü, Yufeng Liu, Yujie Liu, Yujie Liu, Yujie Liu
Abstract
Abstract Osteoarthritis (OA) is a condition associated with severe inflammation, cartilage destruction and degeneration of joints. Rhein (Rh) is an effective anti-inflammatory drug with proven efficacy in in-vitro and in-vivo models. pH sensitive Rh and NH 4 HCO 3 laden poly (lactic-co-glycolic acid (PLGA) nanoparticles (NPs) (Rh-PLGA-NPs@NH 4 ) are developed for an effective treatment of OA. The Rh-PLGA-NPs@NH 4 are prepared along with Rh-PLGA-NPs as a control by double emulsion method. Rh-PLGA-NPs@NH 4 was characterized for their size, shape, morphology and encapsulation efficiency (EE). The effect of pH on release of Rh from Rh-PLGA-NPs@NH 4 was studied at different pH. Further, the cytotoxicity effect of Rh-PLGA-NPs@NH 4 on THP-1 cells were evaluated. Anti-inflammatory efficacy was evaluated on LPS stimulated THP-1 cells and the release of pro-inflammatory cytokines was evaluated and compared with control. The size of Rh-PLGA-NPs@NH 4 and Rh-PLGA-NPs was found to be 190.7 ± 1.2 nm and 134.6 ± 2.4 nm respectively with poly dispersity (PDI) 0.14 and 0.15. The zeta potential of Rh-PLGA-NPs@NH 4 was found to be -22 ± 1.12 mV. Rh-PLGA-NPs@NH 4 were uniform, smooth and spherical shape as confirmed using electron microscopy analysis. Rh-PLGA-NPs@NH 4 release the Rh more effectively in the low pH of synovial fluid environment (SFE). Rh-PLGA-NPs@NH 4 also significantly affect inflammatory cytokines TNF-α and IL-1β and reduced their release in LPS stimulated THP-1 cells. Reactive oxygen species (ROS), a mediator responsible for the cartilage collapse was also found to be reduced. Results proposes that Rh-PLGA-NPs could provide therapeutic solution to those patients who suffer from chronic joint ailments by reducing the progression of OA.