Rhein laden pH-responsive polymeric nanoparticles for treatment of osteoarthritis

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 NH₄HCO₃ laden poly (lactic-co-glycolic acid (PLGA) nanoparticles (NPs) (Rh-PLGA-NPs@NH₄) are developed for an effective treatment of OA. The Rh-PLGA-NPs@NH₄ are prepared along with Rh-PLGA-NPs as a control by double emulsion method. Rh-PLGA-NPs@NH₄ was characterized for their size, shape, morphology and encapsulation efficiency (EE). The effect of pH on release of Rh from Rh-PLGA-NPs@NH₄ was studied at different pH. Further, the cytotoxicity effect of Rh-PLGA-NPs@NH₄ 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@NH₄ 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@NH₄ was found to be -22 ± 1.12 mV. Rh-PLGA-NPs@NH₄ were uniform, smooth and spherical shape as confirmed using electron microscopy analysis. Rh-PLGA-NPs@NH₄ release the Rh more effectively in the low pH of synovial fluid environment (SFE). Rh-PLGA-NPs@NH₄ 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.

Keywords: Anti-inflammatory; Drug delivery; Nano-carriers; PLGA; pH-sensitive.