Abstract
Background
Nanodrug delivery systems offer promising solutions to the limitations of conventional treatments for rheumatoid arthritis (RA) and type 2 Diabetes Mellitus (T2DM). Among nanoparticles, niosomes are particularly effective due to their stability, ease of preparation, and ability to reduce systemic toxicity. They provide controlled drug release and enhance the solubility and stability of pharmaceutical compounds. Incorporating hyaluronic acid (HA) into niosomes can further enhance their efficacy by targeting specific cells, improving drug delivery, and increasing therapeutic impact. In this study, metformin, a common T2DM medication, was effectively delivered using HA-coated niosomes, to demonstrate the potential of this approach in treating RA patients with T2DM.
Methods
Peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of RA patients, RA patients with T2DM, and healthy individuals. Metformin-loaded niosomal nanoparticles (Nio-met NPs) were synthesized using the thin-film hydration method and modified into Hyalo-Nio-met NPs by adding hyaluronic acid. The drug release pattern of metformin was studied, and these NPs were characterized using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Fourier Transform Infrared Spectroscopy (FT-IR). Factors like reactive oxygen species (ROS), interleukin-23 (IL-23), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), receptor activator of nuclear factor kappa-Β ligand (RANKL), and cyclooxygenase-2 (COX-2) were assessed in both treated and untreated PBMCs.
Results
The synthesized Hyalo-Nio-met NPs exhibited a spherical morphology with sizes of 179 ± 8.5 nm, a polydispersity index (PDI) of 0.663, and a zeta potential of -9.76 ± 3.4 mV. FT-IR analysis confirmed the effective encapsulation of metformin within the Hyalo-Nio-met NPs. Approximately 68% of the loaded metformin was released from the Hyalo-niosomal NPs after 120 hours. Treatment with Hyalo-Nio-met NPs led to a significant reduction in reactive oxygen species (ROS) level and decreased activity of pro-inflammatory cytokine (IL-23) and inflammation-related genes (NFATc1, RANKL, and COX-2).
Conclusion
Taken together the Hyalo-Nio-met NPs drug delivery system was acceptable in terms of characteristics and effectively delivery of metformin to the vicinity of PBMCs. The treatment demonstrated a notable reduction in inflammatory markers and an enhancement of anti-inflammatory and antioxidant defenses in the PBMCs from both RA patients and RA patients with T2DM.