The delivery of alpha1-antitrypsin therapy through transdermal route: is this worse to explore?

ABSTRACT: Human α1-antitrypsin (AAT) is an abundant acute phase glycoprotein performing anti-protease, anti-apoptotic and immunomodulatory functions. Purified human plasma AAT used as a specific therapy for patients with lung emphysema and panniculitis due to inherited AAT deficiency, and it is beneficial in treating of other disorders. This therapy administered intravenously although other routes of administration are tested. Herein, we examined the transdermal application of native or recombinant AAT by using epiCS®, the 3D human epidermis equivalent reconstructed from human primary epidermal keratinocytes. Topically applied AAT protein (50µl, prepared in Hank`s balance solution, HBSS) freely diffused across epidermis layers in a concentration and time-dependent manner. We concluded that within 18 hours topically added 0.2 mg AAT well penetrates the stratum corneum and can be detected inside the cytosol of keratinocytes. Importantly, treatments with AAT did not induce obvious morphological changes in keratinocyte layers. Next, we supplemented culture medium with 100µg/ml of combined bacterial lipopolysaccharide (LPS) and peptidoglycan (PNG) mixture and incubated epiCS for 18h with or without the topical application of 0.2 mg AAT. Under these conditions, LPS/PNG triggered a strongly activation of epidermis model. Even though AAT exhibited a limited capacity to neutralize the effect of LPS/PNG, it lowered expression of IL-18 and IL-8, and preserved levels of filaggrin, an important protein for maintaining the epidermal barrier integrity. Our results suggest that the transdermal route for delivering AAT is worth exploration. If successful, this approach may offer easy-to-use therapy with AAT.

ORGANISM(S): Homo sapiens

PROVIDER: GSE150946 | GEO | 2020/05/21

REPOSITORIES: GEO