Angled Insertion of Microneedles for Targeted Antigen Delivery to the Epidermis

Abstract

Peanut and tree nut allergies account for most food-induced anaphylactic events. The standard allergy immunotherapy approach involves subcutaneous injection, which is challenging because severe adverse reactions can occur when antigens spread systemically. Allergen localization within the epidermis (i.e., the upper 20–100 µm of skin) should significantly reduce systemic uptake, because the epidermis is avascular. Microneedle (MN) patches provide a convenient method for drug delivery to the skin, but they generally target both epidermis and dermis, leading to systemic delivery. In this study, we adapted MN technology for epidermal localization by performing angled insertion of 250 µm–long MNs that limits MN insertion depth mostly to the epidermis. We designed a biplanar insertion device to aid the repeatability of angled insertions into porcine skin ex vivo at specified angles (90°, 45°, and 20°). When compared to 90° insertions, MN application at 20° decreased mean insertion depth from 265 ± 45 µm to 97 ± 15 µm. Image analysis of histological skin sections revealed that acute-angle insertion increased epidermal localization of delivery for antigen-coated MNs from 25% ± 13% to 70% ± 21%. We conclude that angled insertion of MNs can target antigen delivery to epidermis.

Exploiting Unique Features of Microneedles to Modulate Immunity

“…[ 170 ] This study, amongst others, provides an example of how MNA design can be tuned to achieve the desired immune response. [ 171 ] Thus, the field is well poised to investigate not only how microneedles can improve delivery compared to conventional routes, but also how MNAs can be improved to achieve the desired immune response.…”

Microneedle systems: cell, exosome, and nucleic acid based strategies

“…This approach reduces systemic uptake, avoids the pain associated with multiple subcutaneous injections, and improves patient compliance. 31–33…”

“…This approach reduces systemic uptake, avoids the pain associated with multiple subcutaneous injections, and improves patient compliance. [31][32][33] 2.3.4 Soluble MN. Soluble MNs are composed of materials that can dissolve or degrade in the body after insertion.…”

“…Fig.4Visual representation of skin layers and three methods of antigen delivery: (a) hypodermic needle injection to the subcutaneous space, (b) perpendicular (i.e., 90°) MN insertion crossing epidermis and into the dermis, and (c) angled MN insertion targeting the epidermis. Reprinted with permission from MDPI,32 Copyright 2022.…”

Soft Injectable Sutures for Dose‐Controlled and Continuous Drug Delivery

“…Transdermal drug delivery using microneedles, for example, offers a relatively painless route of drug delivery through interstitial fluid, where the release of drugs can be sustained over long periods of time and tuned through size, number, and matrix composition of microneedles. [ 2,6–20 ] However, microneedles can still cause skin inflammation, may not penetrate reliably in all skin types, are prone to breakage, and can peel off due to sweating or motion, which makes them highly unreliable for drug delivery. One of the new classes of drug‐delivery systems that is being studied is injectable hydrogels, which allow for painless delivery of therapeutics to desired delivery sites.…”