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

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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.