Non Invasive Ultrasound Assisted Delivery of Drug Loaded Intact Liposomes: A Combined Experimental and Modeling Approach

无创超声辅助载药完整脂质体的递送：实验和建模相结合的方法

• 批准号: 1064802
• 负责人: Peter Lewin
• 金额: $ 33万
• 依托单位: Drexel University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1064802&HistoricalAwards=false
• 关键词: Non; Invasive; Ultrasound; Assisted; Delivery

1064802PapazoglouThe overarching goal of this research is to develop a novel drug delivery technology that provides a wearable, non-invasive, customizable transdermal delivery platform that is not currently available. The technology has the advantage of allowing the intact drug encapsulated in a vesicle to be delivered through the skin layers. This enables sustained, stable release in the systemic circulation and addresses a well-defined clinical need that can lead to improved health outcomes and reduced health care costs. One of the drugs to be tested is used in arthritis and cancer treatment and reducing the side effects and improving its bioavailability with a non-invasive delivery route is of immediate importance. Arthritis affects an estimated 27 million Americans with total costs approaching $55 billion annually. Also, each year over 1.5 million new people are diagnosed with cancer, resulting in direct costs of treatment of $93 billion annually. The interdisciplinary approach combining biochemistry and a non-invasive, non-ionizing modality such as ultrasound to safely deliver any drug without syringes or needles, reduces risk of infection and eliminates patient discomfort. In addition, as it provides a viable clinical alternative to the conventional needle-enabled transcutaneous delivery, it will have an immediate societal impact. The intact drug delivery scheme offers yet another notable advantage over current transdermal delivery methods in that different drug chemistries will not necessitate a new formulation each time a new drug is administered. The proposed technology is truly transformative because it is applicable to a diverse array of drugs and biologics (si-RNA, antibodies, proteins, hydrophobic or hydrophilic molecules). It could lead to industry-wide reevaluation of transdermal delivery techniques and allow clinically relevant toxicity reduction with any drug where clinical efficacy and toxicity levels are very close. In addition to non-invasive, customized drug delivery the proposed wearable patch applicator implementation can be used in applications such as bone healing and nerve stimulation. The novelty of the approach is further amplified by the design of a self-contained, lightweight (100g including battery and driving electronics), flat (10mm in thickness) and fully portable Band-Aid?-like ultrasound applicator. The combined theoretical modeling and experimental (in vitro) approach will aid in determining the optimized set of physico-chemical- and physiological parameters and elucidate the mechanisms that underlie the interaction between the acoustic field, the vesicles and the skin layers. Knowledge of these mechanisms is indispensable in refining the non-invasive transdermal drug delivery methods and designing patient specific individual treatments and will be used in the final design of the wearable patch. The project addresses a well-defined clinical need and will allow drug administration by the patient at home. This will reduce the healthcare expenses by limiting the need for multiple visits at the physician?s office and eliminating the need for frequent patient transportation. At the same time the effectiveness of the treatment will be enhanced by maximizing the patient?s compliance, which in turn will improve health outcomes.

1064802 Papazoglou本研究的总体目标是开发一种新型药物输送技术，提供目前不可用的可穿戴，非侵入性，可定制的透皮输送平台。该技术的优点是允许封装在囊泡中的完整药物通过皮肤层递送。这使得能够在体循环中持续、稳定地释放，并满足明确的临床需求，从而改善健康结果并降低医疗保健成本。其中一种待测试的药物用于关节炎和癌症治疗，通过非侵入性递送途径减少副作用并提高其生物利用度具有直接重要性。 据估计，关节炎影响着2700万美国人，每年的总费用接近550亿美元。此外，每年有超过150万新的人被诊断患有癌症，导致每年930亿美元的直接治疗费用。这种跨学科的方法结合了生物化学和非侵入性、非电离模式（如超声波），可以在没有注射器或针头的情况下安全地输送任何药物，降低感染风险并消除患者不适。此外，由于它提供了一种可行的临床替代传统的针使能经皮输送，它将有一个直接的社会影响。完整的药物递送方案提供了优于当前透皮递送方法的另一个显著优点，因为每次施用新药时，不同的药物化学将不需要新的制剂。所提出的技术是真正的变革，因为它适用于各种药物和生物制剂（si-RNA，抗体，蛋白质，疏水或亲水分子）。它可能导致全行业重新评估透皮给药技术，并允许临床疗效和毒性水平非常接近的任何药物的临床相关毒性降低。除了非侵入性、定制的药物递送之外，所提出的可穿戴贴片施用器实施方式还可以用于诸如骨愈合和神经刺激的应用中。这种方法的新奇进一步放大了一个独立的，重量轻（100克，包括电池和驱动电子），平面（10毫米厚）和完全便携式创可贴？比如超声波施加器结合的理论建模和实验（体外）的方法将有助于确定优化的一组物理化学和生理参数，并阐明了声场，囊泡和皮肤层之间的相互作用的机制。这些机制的知识是必不可少的，在完善非侵入性透皮给药方法和设计患者的具体个人治疗，并将用于可穿戴贴片的最终设计。该项目解决了明确的临床需求，并允许患者在家给药。这将减少医疗费用的限制，需要多次访问的医生？的办公室，消除了频繁的病人运输的需要。在同一时间的治疗效果将通过最大限度地提高病人？这反过来又会改善健康结果。