Crisaborole loaded nanoemulgel for the mitigation of atopic dermatitis in mice model

Abstract

Objective

The present work aims to formulate nanoemulgel of crisaborole (CB) and evaluate its effectiveness against 2,4-Di-nitrochlorobenzene induced (DNCB) atopic dermatitis (AD) in mice.

Significance

AD is a chronic inflammation of the skin affecting the quality of life. CB is a topical PDE4 inhibitor marketed as a 2% ointment. It, however, possesses poor aqueous solubility. An o/w nanoemulsion shall exhibit an enhanced therapeutic effect owing to the increased solubility of CB and an augmented skin penetration. The addition of a gelling agent to form a nanoemulgel further provides ease of application to the patients.

Methods

Nanoemulsion was prepared by aqueous titration method using caproyl PGMC, cremophore EL and propylene glycol as the oil, surfactant, and cosurfactant respectively. The formulations were characterized by their size, zeta potential and polydispersity index (PDI). 1% Carbopol 934 was used as the gelling agent to formulate nanoemulgel comprising of optimized nanoemulsion (NE 9). Ex vivo skin permeation of the CB nanoemulgel was compared with the CB ointment. Its therapeutic effect was evaluated in Balb/c mice.

Results

NE 9 comprised of 7.49% oil, 37.45% S_mix (1:3) and water 55.06%. Its particle size, PDI and zeta potential were 15.45 ± 5.265 nm, 0.098 and −17.9 ± 8.00 mV respectively. The nanoemulgel exhibited a 3-fold higher permeation flux as compared to the ointment. In vivo studies demonstrated that the nanoemulgel provided better therapeutic effect than the ointment.

Conclusion

We can thereby conclude that nanoemulgel formulation can be a successful drug delivery strategy for enhancing the therapeutic effect of CB.

Keywords:

• Nanoemulsion
• nanoemulgel
• crisaborole
• flux
• 2,4-Di-nitrochlorobenzene
• atopic dermatitis

Acknowledgements

The facilities required to conduct the research were provided by Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus, for which the authors are grateful. Crisaborole was donated by Dr Reddy’s Laboratories, Hyderabad.Capryol^® PGMC, caproyl 90, and labrasol were given by Gattefosse (Lyon, France), and cremophore EL and cremophore RH were given by BASF India Ltd (Mumbai, India). The authors also thank Central Instrumentation Facility at I.I.T. B.H. U for TEM studies.

Ethical approval

The animal studies were carried out as per the protocol approved [AUUP/AIP/4/2021(3)] by the Institutional Animal Ethics Committee at Amity Institute of Pharmacy, Amity University, Lucknow. The animal handling guidelines laid down Committee for Control and Supervision on Experimental Animals (CPCSEA), New Delhi, India, were followed.

Disclosure statement

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

Additional information

Funding

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