066 Skin-targeted delivery of crude peanut extracts using dissolving microneedle arrays

Abstract

Peanut allergy is a common IgE-mediated hypersensitivity that has no curative option. Allergen-specific immunotherapy (ASIT) has recently emerged as a promising desensitization approach for several hypersensitivities. True potential of ASIT for peanut allergy has yet to be achieved due to the concerns of efficacy, safety, cost, and convenience of prevailing investigational ASIT methods. Skin-targeted ASIT offers an attractive solution to treatment of peanut allergy since the skin is an easily accessible organ that contains high-density antigen-presenting cells (APCs) and immune-accessory cells. However, it is very challenging to strategically and consistently deliver hydrophilic macromolecule peanut allergens to immune-cell-rich skin microenvironments due to the physical barrier imposed by stratum corneum. Here, we described skin-targeted delivery of crude peanut extracts (CPEs) using dissolving microneedle array(MNA)s toward a safe and effective cutaneous immunotherapy for peanut allergy. Dissolving MNAs integrating CPEs as an alternative to single peanut protein antigens were reproducibly manufactured from a biomaterial composition of Carboxymethlycellulose and Trehalose which are considered safe by FDA. The fabricated MNAs consisted of high-fidelity micron-scale needles incorporating CPEs at their tips that maintained their protein integrity. These MNAs successfully and reproducibly penetrated the skin in mice in vivo and humans ex vivo, dissolved upon penetration, and delivered their biocargoes to APC-rich cutaneous microenvironments. The MNA-delivered CPEs resided in the mouse skin microenvironments for at least 8 hrs in vivo and were present in the skin-draining lymph nodes 48 hr after application. Together, these studies suggest that MNAs could obviate limitations of conventional topical transdermal patches and imprecise hypodermic needle injections to enable the development of an effective cutaneous immunotherapy for peanut allergy.