Iontophoresis to Improve Nail Disease Treatment

描述（由申请人提供）：据估计，约有3000万美国人感染甲癣。目前治疗甲真菌病的方法是口服全身性抗真菌药物，治疗方案长，疗效不高。这种疾病的复发并不罕见，多达四分之一的患者患有持续性甲真菌病。由于肝毒性引起的全身副作用可能很严重，需要定期进行血液检查和肝功能监测。局部外用药物给药的副作用比全身给药少，但由于指甲屏障的阻力，给药并不十分成功。经甲给药治疗指甲疾病一直是制药科学家面临的挑战。本项目的目标是（1）机械量化人指甲离子电渗转运的屏障特性，（2）克服离子电渗局部给药的这一屏障，以及（3）开发用于治疗指甲疾病的离子电渗系统。该项目包括基础研究和转化研究。对人指甲盖屏障特性的系统研究将为药物的经甲膜给药提供新的认识。将研究离子电渗法以增强药物吸收和穿过指甲板的转运。这些结果将用于开发一种经甲电离子导入给药系统。在我们上一个资助期内开发的生物膜离子电渗疗法的方法和理论框架将为将离子电渗递送技术应用于经甲药物递送和指甲疾病治疗提供必要的知识基础和专业知识。 公共卫生相关性：甲真菌病等指甲疾病已经影响了超过3000万美国人，全球用于这些疾病的相关医疗保健支出超过10亿美元。例如，目前治疗甲真菌病的方法是口服全身施用抗真菌剂，这需要长的治疗持续时间（例如，三个月），具有相对低的总治愈率（小于70%），并且具有全身副作用的风险（例如，肝毒性）。经甲电离子导入治疗甲疾病的成功开发将通过改善治疗效果和降低医疗成本而使公众受益。

DESCRIPTION (provided by applicant): It is estimated that approximately 30 million Americans are infected by onychomycosis. The current method of treatment for onychomycosis is oral systemic administration of antifungal agents, which has long treatment regimen and is not very effective. Reoccurrence of the disease is not uncommon, and up to one-fourth of the patients have persistent onychomycosis. Systemic side effects due to hepatic toxicity can be severe and necessitate regular blood tests and liver function monitoring. Local topical drug delivery has fewer adverse effects than systemic administration, but has not been very successful due to the resistive nail barrier. Transungual drug delivery for nail diseases has remained a challenge to pharmaceutical scientists. The objectives of this project are (1) to mechanistically quantify the barrier properties of human nail for iontophoretic transport, (2) to overcome this barrier for topical drug delivery with iontophoresis, and (3) to develop an iontophoresis system for the treatment of nail diseases. This project includes both basic and translational research. The systematic study of the barrier properties of human nail plate will provide new understanding of transungual drug delivery. Iontophoresis will be investigated for enhancing drug uptake and transport across the nail plate. These results will then be used to develop a transungual iontophoretic drug delivery system. The methodology and theoretical frameworks developed in our last funding period for biomembrane iontophoresis will provide the necessary knowledge base and expertise for applying the iontophoretic delivery technology to transungual drug delivery and nail disease treatment. PUBLIC HEALTH RELEVANCE: Nail diseases such as onychomycosis have affected more than 30 million Americans with related healthcare spending on the diseases more than $1 billion worldwide. For example, the current method of treatment for onychomycosis is oral systemic administration of antifungal agents, which requires long treatment duration (e.g., three months), has relatively low total cure rate (less than 70%), and risks systemic side effects (e.g., hepatic toxicity). The successful development of a transungual iontophoretic system for nail disease treatment will benefit the public by improving treatment outcome and reduce healthcare cost.