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Authors & Affiliations
Gizem Aydemir, Paul Johnson, Mehmet Sirin Ozdas, Yitong Li, Mehdi AghiliBehnam, Wolfger von der Behrens, Mehmet Fatih Yanik
Abstract
Our group recently developed a technology for non-invasive hyperconcentrated (1’300x) focal drug delivery to the brain without opening the blood-brain barrier (BBB), reducing off-target effects significantly [1]. This study aims to investigate and improve the dynamics of focally hyperconcentrated drug release mechanisms using focused ultrasound (FUS) technology and ultrasound-sensitive drug carriers. Firstly, to achieve high concentration of drug release, we designed and manufactured ultrasound-sensitive drug carriers using microfluidic technology, allowing us to have control over size and concentration while increasing drug-loading capacity. Subsequently, a custom-built experimental setup and a microfluidic device that mimics brain capillaries are used to study aggregation and uncaging dynamics. Using an engineered ultrasound sequence and incorporating simultaneous passive cavitation and imaging feedback the behavior of drug carriers under focused ultrasound is comprehensively analyzed with respect to ultrasound safety readouts. The effect of acoustic pressure, flow rate, and capillary dimensions on clustering dynamics is examined. Our findings indicate a pressure range for our drug carriers where we can achieve larger and more stable aggregations of drug carriers, facilitating efficient focal drug release with increased drug concentration in the target region. Results show that as the flow rate increases, there is a corresponding need to elevate pressure to maintain stable aggregations. The uncaging results confirm the significance of achieving stable and larger aggregations to increase the amount of focal drug release. These results have significant implications for optimizing targeted drug delivery strategies for central nervous system (CNS) disorders.