Development and Characterization of Leflunomide and Resveratrol Loaded Nanostructured Lipid Carrier Based In-situ Hydrogel System for Effective Management of Rheumatoid Arthritis

Abstract

Purpose

This study aims to improve the therapeutic effect of leflunomide (LEF), an immune-altering drug, and resveratrol (RSV), a polyphenolic compound distributed locally in the body. LEF and RSV were encapsulated in nanostructured lipid carriers (NLCs).

Method

NLCs were prepared by modified thermal homogenization and melt sonication using compritol ATO 888, oleic acid, Tween 80, and PEG 400. A Box-Behnken design (BBD) was utilized to optimize the formulation. The ideal NLC surface was modified by conjugation with chondroitin sulfate (CHS). Chondroitin sulfate-modified NLCs dispersions (CHS-NLCs) were characterized by particle size, PDI, encapsulation efficiency, and zeta potential. Thermosensitive gel was prepared using Pluronic F-127 (PF-127) and Pluronic F-68 (PF-68). Gels prepared in situ based on CHS-NLCs were characterized by gel time, thermal reversibility, pH, viscosity, injection time, and in vitro release. The effectiveness of the NLC-based in situ hydrogels was tested in an arthritis model.

Results

The produced CHS-NLCs had a particle size of 188.2 ± 0.85 nm, PDI of 0.396 ± 0.005, zeta potential of -17.16 ± 0.81 mV, LEF and RSV encapsulation efficiency of 92.16 ± 0.41 and 82.82%, respectively. The gel was thermosensitive and released 79.54% and 76.99% of LEF and RSV, respectively, within 144 h. The effectiveness of the proposed method was tested using an arthritis model, and the results showed a reduction in joint pain in mice in 21 days.

Conclusion

The developed CHS-modified NLC-based in situ hydrogel demonstrated effective, sustained drug release and significant therapeutic benefits in an RA model. This approach holds promise for improved RA management through localized drug delivery.