Enhanced dermal penetration of cyclosporine a from a nano-gel formulation for the treatment of alopecia

Alopecia areata(AA) is an autoimmune disease manifesting itself as a single or multiple patches of non-scarring hair loss, commonly observed on the scalp[1]. The disease has a noticeable impact on the patient’s appearance and influence his quality of life. Oral cyclosporine A(CsA) was shown to be clinically effective in the treatment of AA. However, severe adverse-effects may restrict its use. Despite of its common adverse effects like nephrotoxicity and hypertension, CsA offers good safety profile when used in skin diseases. Unfortunately, owing to its large molecular weight and poor water solubility, CsA penetration into skin following topical application is limited. Nevertheless,the promise of CsA delivery into the intact skin mediated by various nanocarriers is encountering more and more success[2]. The objective of the present study is to design an effective topical delivery system of CsA for the treatment of AA. For such a purpose, since no animal model exits for AA efficacy evaluation, it was decided to use the mouse model of androgenetic-alopecia(AGA)which is characterized by progressive hair loss caused by androgenetic miniaturization of the hair follicle[3].

Following formulation screening, adequate experimental conditions were identified for the incorporation of CsA in a nanoemulsion suspended in a gel formulation for the treatment of AGA. Prolonged accelerated stability tests were carried out to ensure that CsA remained stable while the aqueous gel formulation maintained the non-Newtonian rheological properties over three months. Moreover, the ex-vivo human skin penetration assay results in Franz cells showed an enhancement and significant levels of CsA in the dermis of the aqueous gel compared to the CsA oil solution. Finally, the animal experiments performed using AGA induced in C57BL/6 mice according to the ethical committee approval guidelines demonstrated that CsA nano-gel formulation significantly enhanced hair growth compared to non-treated animals.

References

[1] Wasserman D,Guzman DA,et al.Alopecia areata.Int J Dermatol.2007;46:121–31.

[2] Badihi A,Frušić-Zlotkin M,et al.Topical nano-encapsulated cyclosporine formulation for atopic dermatitis treatment.Nanomedicine:2020;24:102-14.

[3] Crabtree JS,Kilbourne EJ,et al.A mouse model of androgenetic alopecia.Endocrinology.2010;151:2373-80