Topical nano-encapsulated cyclosporine formulation for atopic dermatitis treatment

Systemic cyclosporine A (CsA) therapy shows efficacy in the treatment of recalcitrant severe atopic dermatitis (AD) but elicits severe side-effects. Thus, a topical formulation of CsA nanocapsules (NCs), able to potentially bypass these drawbacks, was developed. CsA-NCs were shown to enhance drug penetration into the various layers of porcine ear skin. Furthermore, the encapsulated CsA was biologically active, as shown in vitro on mouse splenocytes, reflected by inhibition of both cell proliferation and of interleukin (IL)-2 secretion. Ex-vivo efficacy was demonstrated on human skin organ culture by markedly reducing pro-inflammatory cytokines secretion. Finally, CsA-NCs topical formulation elicited improved efficacy in terms of better preservation of the skin barrier integrity, a decrease of the systemic pro-inflammation markers and reduced skin inflammation. The overall results suggest that this original topical platform may provide a novel therapeutic tool of clinical significance compared to the existing topical therapeutic drugs in AD. Adequate experimental conditions were identified for the formulation of a stable nanocapsules of cyclosporine A. The dermal penetration of CsA was evaluated on pig skin, showing high drug levels in the epidermis and dermis. LPS-induced inflammation in human skin specimens showed high levels of IL-6 and IL-8, as well as with blank NCs, whereas 15 µg/cm2 CsA NCs showed significant reduction in both cytokines' levels, evidencing the release of CsA within the skin. Finally, an in vivo study of OVA-induced AD showed that CsA NCs elicited the most effective results as compared to CsA ointment, and other commercial products. [Display omitted]