الحالة الالتهابية المضادة للالتهابات والأكسدة لدى النساء المصابات بالتهاب المفاصل الرثوي والمرضى المصابين وغير المصابين بمرض السكري من النوع الثاني وتأثير الميتفورمين النانوي على خلايا الدم المعزولة

Inflammatory Anti- Inflammatory and Oxidative Status in Rheumatoid Arthritis Women Patients with and without Type Two Diabetes and the Effect of Nanoformulated Metformin on Isolated Blood Cells

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovitis, cartilage damage, and bone erosions, which is associated with increased morbidity and mortality compared with the general population. Systemic inflammation associated with RA might contribute to the risk of developing diabetes in the future. RA is associated with chronic inflammation, which might, at least in part, trigger the development of type 2 Diabetes Mellitus (T2DM). Nano-drug delivery systems offer promising solutions to the limitations of conventional treatments for RA and 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. Metformin, a common T2DM medication was effectively delivered using HA-coated niosomes, demonstrating the potential of this approach in treating RA and T2DM.
This study aims to determine the inflammatory/anti-inflammatory biomarkers to early detection of RA and prognosis to prevent the development of T2DM, association and correlation between variables markers that correlate with disease, and using metformin, a common T2DM medication, effectively delivered using HA-coated niosomes, to demonstrate the potential of this approach in treating for RA and T2DM by using a molecular method of PCR of various factors, such as total oxidant status (TOS), interleukin-23 (IL-23), nuclear factor of activated T-cells cytoplasmic 1 (NFATC1),and receptor activator of nuclear factor kappa-Β ligand (RANKL), was assessed in both treated and untreated Peripheral blood mononuclear cells (PBMCs).
A case-control study was performed on 118 participants divided into 47 as healthy control, 71 as RA patients 33 RA patients with T2DM, and 38 RA without T2DM, all patients with rheumatoid factors positive test. They were all directly interviewed and blood samples were taken. Age at the onset of RA plays an important role in determining the severity of the disease and its development, especially for those between (40-49) years of age (42.3%). This indicates that these age-related factors are crucial for developing effective therapeutic strategies and managing comorbidities in patients with rheumatoid arthritis. Patients suffering from obesity were more likely to develop RA and their percentage was (43.7%) compared to those from the other groups. This indicates a positive relationship between body mass index (BMI) and the risk of developing RA
In the case of RA with T2DM patients had significantly higher Fasting blood sugar (FBS)(331.30 ± 108.84 mg\dL) levels as compared to RA patients without T2DM(106.92 ± 8.17mg\dL) (P-value < 0.001), indicating impaired blood sugar control, while the glycated hemoglobin HbA1c(5.52 ± 0.64%) a marker for long-term blood sugar control, was significantly elevated in the RA withT2DM group (11.80 ± 1.81% ) (P-value < 0.001) this relationship indicates the prognostic importance to monitoring and preventing the development of T2DM in patients of RA. The exogenous antioxidants such as vitamin E related to the reduction of blood glucose as well as glycated hemoglobin as compared with chemical drugs. The result observed that vitamin E and selenium non-significantly decreased RA patients with and without T2DM (P>0.05). Results indicated a highly statistically significant difference in IL-23 and Transforming Growth Factors – Beta (TGF-β) levels among groups, The mean levels of IL-23, TGF-β in patients in RA (41.32 ± 14.15pg\mL), ( 40.56 ± 16.35pg\mL) respectively, significantly higher than for the Control group(9.16 ± 1.01 pg\mL),( 4.42 ± 2.79 pg\mL) respectively. The results show highlights the potential of hyaluronic acid-coated niosomal nanoparticles as an effective drug delivery system for metformin, targeting RA and T2DM-derived PBMCs. The Hyalo-Nio-met NPs exhibited desirable characteristics, including stability and controlled drug release. The incorporation of HA enhanced the targeting and therapeutic impact of these niosomes. The synthesized Hyalo-Nio-met NPs showed a significant reduction in TOS, the pro-inflammatory cytokine IL-23 inflammation-related genes NFATC1, and RANKL in PBMCs from RA patients. This indicates a promising reduction in inflammation and enhancement of anti-inflammatory and antioxidant defenses. Overall, the Hyalo-Nio-met NPs drug delivery system effectively delivered metformin to PBMCs, showing potential as a novel therapeutic approach for RA and T2DM by reducing systemic toxicity and improving drug delivery to specific cells.