In-Vitro and in-Vivo Evaluation of the Developed Curcumin-Cyclosporine-Loaded Nanoemulgel for the Management of Rheumatoid Arthritis

ABSTRACT

Background

Topical nanogel-based formulations have shown potential in the management of rheumatoid arthritis (RA). The aim of this research work was to explore the synergistic effect of Curcumin (CUR) and Cyclosporine (CYC) in combination via a topical route for the management of RA.

Methods

The CUR+CYC loaded nanoemulsion was developed using the spontaneous emulsification technique and was subsequently incorporated into Carbopol® Ultrez 30-NF gel. The effect of the developed formulation on levels of proinflammatory cytokines (IL-6, TNF-α) and anti-inflammatory cytokine (IL-10) was evaluated using lipopolysaccharide (LPS) induced RAW 264.7 cell culture model. The anti-arthritic activity was evaluated in a Complete Freund’s Adjuvant (CFA) induced arthritic rat model.

Results

The optimized nanoemulgel (CUR + CYC NE gel) exhibited average globule size of 15.32 nm ±2.7 nm, poly-dispersity index of 0.181 ± 0.034 and zeta potential of −16.3 mV ± 0.9 mV. The cumulative drug release from ex-vivo diffusion studies on porcine ear skin was 99.189% ± 1.419% at the of 24 h and 99.177% ± 1.234% at the end of 18 h for CUR and CYC, respectively. The cell culture studies revealed that the formulation was able to significantly lower (p < .001) the levels of IL-6 and TNF-α, inhibited prostaglandin E2 (PGE2) while significantly elevating (p < .001) the levels of anti-inflammatory cytokine (IL-10). The gel was found to be non-irritating and showed the inhibition of paw edema and substantial reduction of arthritic symptoms in an arthritic rat model as compared to commercial and other conventional alternatives.

Conclusion

This study highlights the potential of the developed nanoemulgel for the management of RA by enhancing the topical permeation of CUR and CYC.

GRAPHICAL ABSTRACT

KEYWORDS:

• Arthritic rat model
• curcumin
• cyclosporine
• nanoemulgel
• rheumatoid arthritis

Acknowledgments

The authors thank the Department of Science and Technology (DST) Fund for Improvement of S & T Infrastructure in Universities and Higher Educational Institutions (FIST) (SR/FST/College-054/2017) for funding the research facilities which were utilized for the current research.

Author contribution

Sankalp Gharat has conceptualized, designed, conducted, collected and analysed the data and has drafted the manuscript. Vivek Basudkar has helped in drafting the manuscript. Dr. Munira Momin has guided this research project and has reviewed the manuscript.

Ethics approval

Animal study protocol was approved by the Institutional Animal Ethics Committee (IAEC) (Approval number – CPCSEA/IAEC/P-06/2022).

Consent for publication

Yes

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.