Lightweight Electronically Controlled Transdermal Patch for Enfuvirtide Delivery

描述（由申请人提供）：该I期NIH SBIR将开发用于恩福韦肽递送的轻型电子控制透皮贴剂（LET-PED）。全世界有3300万人感染了人类免疫缺陷病毒（HIV）。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治疗方案在药物数量、每天剂量和不良反应方面可能很复杂。治疗艾滋病毒的药物治疗方案必须几乎完全遵守，以最大限度地提高疗效并防止病毒耐药性的发展。Enfuvirtide于2003年获得美国食品和药物管理局（FDA）的批准，是一种输注抑制剂，可以阻止HIV病毒附着在CD4细胞（或t细胞）上。它每天皮下注射两次，用于对其他治疗无效的患者。然而，已经发现98%的患者会出现注射部位反应。压电超声经皮给药技术已经在动物模型和人体试验中被证明可以给药胰岛素。20千赫的超声波在角质层中打开25到125米的微通道，允许药物到达血液系统，但在低强度水平下工作，通过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、自动和安全的超声波给药装置，使艾滋病患者遵守药物治疗制度。第一阶段的具体目标是：设计并制造了一种具有可更换/可再填充储药库和压电微泵的压电轻质换能器给药贴片。2. 用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度。使用含有恩孚韦肽的人体皮肤样本进行声学实验，以评估LET-PED的穿透性。这些目标将验证压电透皮给药贴片可以让恩孚韦肽通过皮肤而不会造成组织损伤的假设。这项工作的长期目标是使LET-PED商业化。西欧和北美约200万艾滋病患者将是第一个目标市场。该技术还可以获得特定应用领域的许可。公共卫生相关性：NIH SBIR一期研究将开发一种用于恩福韦肽递送的轻型电子控制透皮贴片。LET-PED将是一种无针、自动和安全的超声波给药装置，使艾滋病患者遵守药物治疗制度。

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.