Ultrasonic analysis of precision-engineered acoustically active lipospheres produced by microfluidic

摘要

The development of a ¿magic bullet¿ that could carry therapeutic dose of drug to a target organ or tumor with high specificity is the ideal goal of targeted drug delivery. Acoustically active drug carriers must possess a layer with drug-carrying capacity, similar to a liposome, yet at the same time, they must have a core with significantly different density and compressibility than the surrounding media - such as a gas. Factors such as consistent response to acoustic pulses and consistent loading per particle are important characteristics for reliable delivery. Here, we utilize microfluidic technology to precision engineer acoustically-active drug delivery vehicles. Microfluidic multi-layer flow focusing enables production of acoustically active lipospheres (AALs) with nearly identical diameter. We perform ultrasonic interrogation of these multi layer vehicles as they are produced to determine their acoustic activity and diameter consistency. Acoustic response from lipospheres was measured to be on the same order of magnitude as responses from thin-wall lipid shelled contrast agents, indicating the oil layer did not produce notable damping effects on the acoustic scattering. We hypothesize that based on nearly identical echo signatures, that it will be easier to optimize ultrasound radiation-force mediated concentration and acoustically-mediated drug release to affect all AALs similarly.