Preparation, Characterization and <i>in vitro</i> Pharmacological Evaluation of PLGA-Encapsulated Tofacitinib Nanoparticulate Drug Delivery Systems for the Treatment of Rheumatoid Arthritis

Tofacitinib (Tof), a JAK3 inhibitor, is clinically utilized for the treatment of moderate to severe rheumatoid arthritis (RA). However, long-term oral administration of Tof can lead to serious systemic toxicity and adverse effects. To mitigate its toxicity, this study prepared drug-loaded nanoparticles (NPs), PLGA@Tof, utilizing poly (lactic-co-glycolic acid) PLGA as the matrix. These NPs exhibited a particle size of 220[Formula: see text]nm, a zeta potential of −13.4[Formula: see text]mV, drug loading and encapsulation efficiency were 4.12% and 40.57%, and a smooth spherical morphology. In vitro studies demonstrated that these NPs achieved sustained release of Tof without inducing hemolytic effects; less than 50% Tof was released within 24[Formula: see text]h under [Formula: see text]H 5.0 and [Formula: see text]H 7.4 conditions. Cellular experiments revealed that the uptake rates of NPs at 1[Formula: see text]h, 2[Formula: see text]h, 4[Formula: see text]h and 8[Formula: see text]h in RAW264.7 cells were significantly higher than that of the free drug under inflammatory conditions. After 8 h of treatment with PLGA@Tof on inflammatory RAW264.7 cells, the intracellular reactive oxygen species (ROS) level was significantly lower compared to the free Tof treatment group, while the levels of TNF-[Formula: see text], IL-1 [Formula: see text] and IL-6 were also significantly reduced in the PLGA@Tof treatment group. These findings suggest that PLGA@Tof has the potential to be developed into a long-acting nanotherapeutic agent for systemic or localized injection in the treatment of RA.