Targeted Delivery to the Epidermis Via Angled Insertion of Microneedles

Peanut allergies affect 1 - 2% of adults and 4 - 8% of children. A traditional method for treating peanut allergies is by allergy shots, formally known as subcutaneous allergen immunotherapy (SCIT). This approach is daunting for young children as they are often afraid of injection by needle. Also, SCIT with antigens such as Arachis hypogaea 2 (Ara h 2), the dominant peanut allergen, can result in severe allergic immune responses—in some cases, even anaphylaxis. One of the main reasons for these adverse effects is rapid clearance of antigens by macrophages in the dermis and subcutaneous layers of the skin.

The safety and efficacy of targeting allergen-specific immunotherapy to the skin can be augmented by increasing the localization of the antigen in the epidermis, therefore decreasing the amount localized in the dermis/subcutaneous layers. Microneedles (MNs) have a geometry that allows for antigen delivery targeted to epidermal thickness (30 - 140 µm). They also provide a solution to the pain associated with SCIT. In addition, MNs circumvent patient compliance issues caused by needle phobia.

This study employs angled insertion of 250 μm long MNs (coated with Ara h 2-containing solution) into the skin for the purpose of maximizing antigen localization in the epidermis. Three angles of insertion (relative to the plane of the skin) were studied: 90° (straight insertion), 45°, and 20°. Stainless steel MN arrays are first dip-coated on a micron-scale with a fluorescent Ara h 2 solution. Angled (45° and 20°) MN insertions were executed using a biplanar, 3D-printed device with an adjustable angle of elevation while straight insertions were performed by hand. These pieces of skin were then histologically sectioned, and the insertion sites were imaged with red fluorescence under a microscope. Finally, the sections were H&E stained and imaged under a bright-field microscope to differentiate the layers of the skin.

These data show that angled insertion was successful to limit MN insertion depth to facilitate targeted delivery to epidermis. We also include fluorescent and companion H&E-stained images of representative insertion sites, which together give insight on the extent of epidermal targeting. Opportunities for further study include in vivo insertions on porcine/murine subjects and immunohistochemistry to measure specific antigen localization in the epidermis.