Atopic dermatitis and psoriasis are the two most common chronic inflammatory skin diseases. There is an unmet medical need to overcome limitations for transcutaneous drug development posed by the skin barrier.
We aimed to identify a novel transdermal delivery peptide and to develop a transcutaneously applicable immunomodulatory protein for treating atopic dermatitis and psoriasis.
We identified and generated reporter proteins conjugated to AP, a novel transdermal delivery peptide of human origin, and analyzed the intracellular delivery efficiency of these proteins in mouse and human skin cells and tissues using multi-photon confocal microscopy. We also generated a recombinant therapeutic protein, AP-rPTP, consisting of the phosphatase domain of T cell protein tyrosine phosphatase (TC-PTP) conjugated to AP. The immunomodulatory function of AP-rPTP was confirmed in splenocytes upon cytokine stimulation and TcR stimulation. Finally, we confirmed the in vivo efficacy of AP-rPTP transdermal delivery in OXA-induced contact hypersensitivity, OVA-induced atopic dermatitis-like, and imiquimod-induced psoriasis-like skin inflammation models.
AP-conjugated reporter proteins exhibited significant intracellular transduction efficacy in keratinocytes, fibroblasts, and immune cells. In addition, transcutaneous administration of AP-dTomato resulted in showed significant localization into the dermis and epidermis in both mouse and human skin. AP-rPTP inhibited pSTAT1, pSTAT3, and pSTAT6 in splenocytes and also regulated T cell activation and proliferation. Transcutaneous administration of AP-rPTP via the paper-patch technique significantly ameliorated skin tissue thickening, inflammation, and cytokine expression in both atopic dermatitis-like and psoriasis-like dermatitis models.
We identified a 9-amino acid-long novel transdermal delivery peptide, AP, and demonstrated its feasibility for transcutaneous biologic drug development. Moreover, AP-rPTP is a novel immunomodulatory drug candidate for human dermatitis.
Key words : Atopic dermatitis; psoriasis; transdermal delivery peptide; protein tyrosine phosphatase; TC-PTP; transcutaneous drug; immunomodulatory protein