Iontophoresis to Improve Nail Disease Treatment

描述（由申请人提供）：据估计，大约有3000万美国人感染了甲真菌病。目前治疗甲真菌病的方法是全身口服抗真菌药物，治疗周期长，效果不太好。这种疾病的复发并不罕见，高达四分之一的患者有持续的甲真菌病。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。局部局部给药的不良反应比全身给药少，但由于指甲的抵抗性屏障，并不是很成功。经口给药治疗指甲疾病一直是制药科学家面临的一个挑战。该项目的目标是：(1)机械量化人体指甲离子导入运输的屏障特性，(2)克服离子导入局部药物递送的障碍，(3)开发用于治疗指甲疾病的离子导入系统。该项目包括基础研究和转化研究。对人甲板屏障特性的系统研究将为经口给药提供新的认识。离子透入将被研究以增强药物在甲板上的吸收和运输。这些结果将用于开发一种跨舌离子渗透给药系统。生物膜离子透入的方法和理论框架将为离子透入技术应用于经舌药物传递和指甲疾病治疗提供必要的知识基础和专业知识。

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.