Lightweight Electronically Controlled Transdermal Patch for Enfuvirtide Delivery

描述（由申请人提供）：本I期NIH SBIR将开发一种用于恩夫韦肽给药的轻型电子控制透皮贴剂（LET-PED）。全世界有3 300万人感染了人体免疫缺陷病毒（艾滋病毒）。目前，感染艾滋病毒的患者接受高效抗逆转录病毒治疗（HAART）来控制感染。HAART方案在药物数量、每天剂量和不良反应方面可能很复杂。艾滋病毒管理的药物治疗方案必须采取近乎完美的遵守，以最大限度地发挥效益，防止病毒耐药性的发展。恩夫韦肽于2003年获得美国食品和药物管理局（FDA）批准，是一种输注抑制剂，可阻止HIV附着在CD 4细胞（或T细胞）上。它每天皮下注射两次，针对对其他治疗无反应的患者。然而，已经发现98%的患者经历注射部位反应。压电超声透皮给药技术已被证明在动物模型和人体试验中递送胰岛素。20 kHz的超声波在角质层中打开25至125 μ m的微通道，使药物能够到达血液系统，但在低强度水平下运行，使用组织学检查没有显示任何明显的损伤或显著的皮肤变化。LET-PED将是一种无针，自动和安全的超声药物输送设备，以保持艾滋病毒患者的药物治疗方案的依从性。第一阶段的具体目标是：1。设计并构建具有可更换/可再填充药物储存器和压电微型泵的压电传感器轻质药物输送贴片。2.通过组织学和共聚焦显微镜研究表征声能场并确定对皮肤的安全限值3.使用恩夫韦肽人体皮肤样本进行声学实验，以评估使用LET-PED的渗透性。这些目的将测试压电透皮给药贴剂可以允许恩夫韦肽通过皮肤而不引起组织损伤的假设。这项工作的长期目标是使LET-PED商业化。西欧和北美约200万艾滋病毒患者将成为第一个目标市场。该技术也可以被许可用于特定的应用领域。公共卫生相关性：该I期NIH SBIR将开发一种用于恩夫韦肽给药的轻型电子控制透皮贴剂。LET-PED将是一种无针、自动和安全的超声药物输送设备，以保持艾滋病毒患者的药物治疗方案依从性。

DESCRIPTION (provided by applicant): This Phase I NIH SBIR, will develop a Lightweight Electronically Controlled Transdermal Patch for Enfuvirtide Delivery (LET-PED). Thirty-three million people worldwide are living with the Human Immunodeficiency Virus (HIV). Currently, patients infected with HIV receive Highly Active Antiretroviral Therapy (HAART) for the management of the infection. HAART regimens can be complex in terms of numbers of medications, number of doses per day, and adverse effects. Medication regimens for the management of HIV must be taken with near perfect compliance to maximize benefits and prevent the development of viral resistance. Enfuvirtide, approved by the Food and Drug Administration (FDA) in 2003, is an infusion inhibitor that blocks the HIV from attaching to the CD4 cell (or T-cell). It is subcutaneously injected twice daily and directed at patients not responding to other treatments. However, it has been found that 98% of patients experience injection site reactions. Piezoelectric ultrasonic transdermal drug delivery technologies have been shown to delivery insulin in animal models and human trials. The 20 kHz ultrasonic waves open 25 to 125 ¿m micro-channels in the stratum corneum, allowing the medications to reach the blood system, but operate at low intensity levels that did not show any noticeable damage or significant skin change using histological examination. The LET-PED will be a needle-free, automatic and safe ultrasonic drug delivery device to keep HIV patients in medication regime compliance. Phase I Specific Aims are: 1. Design and build a piezoelectric lightweight transducer drug delivery patch with a replaceable/refillable drug reservoir and piezoelectric micro-pump. 2. Characterize the acoustic energy field and determine the safety limits to skin with histological and confocal microscopy studies 3. Perform acoustic experiments using human skin samples with Enfuvirtide to evaluate the penetration using the LET-PED These aims will test the hypothesis that that a piezoelectric transdermal drug delivery patch can allow Enfuviritide to pass through the skin without causing tissue damage. The long-term objective of this work is to commercialize the LET-PED. The HIV population of ~2 million patients in Western Europe and North America would be the first target market. The technology could also be licensed for specific application areas. PUBLIC HEALTH RELEVANCE: This Phase I NIH SBIR, will develop a Lightweight Electronically Controlled Transdermal Patch for Enfuvirtide Delivery. The LET-PED will be a needle- free, automatic and safe ultrasonic drug delivery device to keep HIV patients in medication regime compliance.