Acousto-chemical manipulation of drug distribution: In vitro study of new drug delivery system

Abstract

In vitro experiments were conducted for developing a novel drug delivery system (DDS). In the previous study, we achieved destruction of tissue structures by the combined use of pulsed ultrasound and liquid microbubble precursors, i.e., phase change nanodroplets (PCNDs). Here, fundamental studies were carried out to investigate the possibility of a DDS utilizing the phenomena. Gels with aqueous regions filled with PCNDs and sham drugs (black ink particles) were used as tissue mimicking samples with locally injected PCNDs and drugs. The exposure of samples to focused ultrasound pulses at 1.1 MHz with an acoustic intensity of 3.2 kW/cm2 was found to cause the transport of the sham drug toward the transducer. The transport speeds were about 0.34 and 0.1 mm/s, in and out of the focal zone of the transducer, respectively. Focal zone shifting during the exposure with an appropriate timing resulted in an enhanced drug transport while maintaining the initial speed of 0.34 mm/s. Our results suggested that the spatial distribution of locally injected drugs can be manipulated using ultrasound pulses when drugs are injected with PCNDs. As a control experiment, the effect of Sonazoid®, a commercially available microbubble contrast agent, was investigated. No drug transport was observed using Sonazoid® at a bubble number density one order of magnitude higher than that used in the PCND experiments. The pressure resistance properties of PCND and Sonazoid® might be related to the absence of the drug transport phenomena in case of Sonazoid®.