Kamimura Mitsuhiro, Todo Hiroaki, Sugibayashi Kenji, Asano Koichiro
Department of Respiratory Medicine, National Hospital Organization Disaster Medical Center, Tokyo 190-0014, Japan.
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
Pharmaceutics. 2025 Jul 2;17(7):867. doi: 10.3390/pharmaceutics17070867.
Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid's unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications.
局部经皮给药最近已成为治疗过敏性疾病的一种新策略，可将药物靶向递送至皮肤附近的黏膜组织。与作用于皮肤表面或黏膜的传统局部给药方法不同，局部经皮给药能够对结膜、鼻黏膜和气管等更深层结构进行非侵入性药理调节。本综述探讨了经皮治疗在过敏性结膜炎、过敏性鼻炎和哮喘相关性咳嗽中的理论依据、药代动力学基础、临床数据及未来前景。在过敏性结膜炎中，基于眼睑的抗组胺药如苯海拉明和依匹斯汀经皮给药已显示出能快速且持久地缓解症状，依匹斯汀乳膏最近在日本获批，此前一项随机对照试验（RCT）证明了其疗效。临床前和临床药代动力学研究支持眼睑独特的通透性和持续药物释放特性，强化了其作为眼部治疗给药部位的实用性。在过敏性鼻炎中，对鼻翼应用苯海拉明可使不耐受鼻内治疗的患者症状得到改善，尽管与发炎鼻甲的解剖分离可能会限制疗效的一致性。同样，在哮喘相关性咳嗽中，对颈段气管应用类固醇和抗组胺药已显示出潜在益处，特别是对于吸入治疗无效的患者，尽管存在解剖学和深度相关的局限性。总体而言，特定部位的解剖结构、皮肤通透性和疾病定位是决定治疗效果的关键因素。虽然经眼睑治疗有充分的数据支持，但对鼻翼和气管的研究仍限于小规模的试点试验。鼻内或气管应用尚未报告重大不良事件，但眼睑敏感性要求在制剂方面谨慎。为验证这种有前景的给药方式，有必要进行进一步的随机对照试验、药代动力学分析和制剂优化。局部经皮给药有望成为一种非侵入性、靶向性的替代方法，用于治疗皮肤科以外的过敏性疾病。
