Pharmacological Evaluation of Iguratimod Loaded Nanostructured Lipid Carriers in Freund’s Complete Adjuvant-Induced Rheumatoid Arthritis in Rats: Anti-Inflammatory, Biochemical, and Histopathological Insights (Research Article)

Author(s): Amit Kumar Pandey* and Amit Kumar

Abstract: Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disorder with limited treatment options due to drug-related toxicities and poor bioavailability. This study evaluated the in vivo anti-arthritic and anti-inflammatory efficacy of optimized Iguratimod-loaded nanostructured lipid carriers (IGU-NLCs) in Freund’s complete adjuvant (FCA)-induced arthritis in Wistar rats. Methods: Acute oral toxicity was assessed per OECD-423 guidelines. Hyaluronidase inhibition assay was performed. Anti-inflammatory activity was evaluated using carrageenan-induced paw edema (1–6 h). RA was induced by intra-articular injection of FCA (0.1 ml) into the left ankle joint on day 0. Female Wistar rats (n=6/group) were divided into normal, control (FCA + normal saline), standard (Indomethacin 10 mg/kg i.p. or MHP 200 mg/kg p.o.), and test (optimized IGU-NLCs 200 mg/kg p.o.) groups. Paw edema, body weight, hematological parameters (Hb, ESR, WBC, RBC), biochemical markers (SGOT, SGPT, total protein, creatinine, uric acid, BUN), serum nitric oxide (NO), vascular permeability (Evans blue extravasation), behavioral parameters (ambulatory activity, rearing), and histopathology of ankle joints were evaluated over 35 days. Results: Acute toxicity study showed no mortality at 2000 mg/kg. IGU-NLCs inhibited hyaluronidase activity by 61.42% at 200 mg/ml. In carrageenan-induced paw edema, IGU-NLCs significantly reduced paw volume at 6 h (0.372 ± 0.074 ml vs. control 0.705 ± 0.079 ml, p < 0.05). In FCA-induced arthritis, IGU-NLCs significantly reduced paw edema from 2.721 ± 0.025 ml (control) to 1.202 ± 0.021 ml (p < 0.001) at day 21. Body weight loss in control (−30.51 g) was attenuated by IGU-NLCs (−19.0 g). Hematological parameters showed improvement. Biochemical parameters confirmed no hepatotoxicity or nephrotoxicity. Serum NO was reduced by 22.45% (p < 0.05). Vascular permeability was inhibited by 33.02% (p < 0.05). Behavioral studies showed partial recovery of ambulatory activity and rearing. Histopathology revealed mild protection (score 3) compared to severe damage in control (score 5). Conclusion: Iguratimod-loaded NLCs demonstrated significant anti-arthritic and anti-inflammatory activity in the FCA-induced rat model, with improved safety profile and partial restoration of behavioral and histological parameters, supporting their potential as an effective nanomedicine for rheumatoid arthritis.

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