Controlled drug release from ultrasound-visualized elastic eccentric microcapsules using different resonant modes

Abstract

Ultrasound controlled drug delivery and release has attracted increased attention for targeted delivery of drug. In this report, we present a strategy for targeted drug delivery by using ultrasound to image the location of drug carriers, as well as simultaneously controlling the release rate of drug from elastic eccentric microcapsules (EEMs), based on their mode shapes (MSs) and resonant natural frequencies (NFs). We prepared a series of EEMs with various diameters of inner spherical cavities using a microfluidic chip. The EEMs could be visualized by an ultrasound imaging system within a tissue mimic (i.e. phantom). Using theoretical modeling techniques, we investigated the effects of MSs and NFs on the resonant modes of EEMs. Guided by this modelling, we applied external ultrasonic stimuli at various levels of low frequency to regulate the release rate of Rhodamine 6G (R6G, as a model drug) from EEMs. To further demonstrate the control of drug release and evaluate the efficacy of the encapsulated drugs on cancer cells, we released an anticancer drug, doxorubicin hydrochloride (DOX), from the EEMs and tested the viability of cancer cells in vitro. The results show that this novel strategy holds great promise towards development of a controlled drug release system visualized and triggered by ultrasound.