Murty Rohan, Sankaranarayanan Abishek, Bowland Isabella I, Mena-Lapaix Juan, Prausnitz Mark R
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Pharmaceutics. 2022 Feb 1;14(2):347. doi: 10.3390/pharmaceutics14020347.
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.
花生和坚果过敏是大多数食物诱发过敏反应事件的主要原因。标准的过敏免疫疗法是皮下注射，这具有挑战性，因为当抗原全身扩散时可能会发生严重的不良反应。由于表皮无血管，将过敏原定位在表皮内（即皮肤上层20 - 100微米）应能显著减少全身吸收。微针（MN）贴片为药物经皮递送提供了一种便捷方法，但它们通常靶向表皮和真皮，导致全身递送。在本研究中，我们通过以一定角度插入250微米长的微针来改进微针技术以实现表皮定位，这种插入方式可将微针插入深度主要限制在表皮。我们设计了一种双平面插入装置，以帮助在体外以特定角度（90°、45°和20°）将微针重复插入猪皮肤。与90°插入相比，20°插入微针时平均插入深度从265±45微米降至97±15微米。对皮肤组织切片的图像分析显示，锐角插入使包被抗原的微针对表皮的递送定位从25%±13%增加到70%±21%。我们得出结论，微针的角度插入可将抗原递送至表皮。
