Visually controlled pulsatile release of insulin from chitosan poly-acrylic acid nanobubbles triggered by focused ultrasound.

Insulin therapy is the most effective way to control the blood glucose value of diabetic patients. The most effective administration route for insulin is subcutaneous injection because bioavailability for non-injection administration is low and unstable. However, patients often need a multiple daily insulin injection regimen to control basal and postprandial blood glucose, which causes various complications. Controlled pulsatile drug release technology using ultrasound as an external stimulus source is a very promising method to avoid multiple injections of insulin. However, most of the drug-loaded microbubbles used for ultrasound-mediated treatment have a short half-life, which limits their use in controlled pulsatile drug release. More importantly, how to control insulin release is still a challenge. In this paper, chitosan poly-acrylic acid nanobubbles as drug carriers of insulin were prepared to achieve a visually controlled pulsatile release of insulin triggered by focused ultrasound. The experimental results in vivo demonstrated that nanobubbles were stable enough to achieve long-term visualization for 7 days after intramuscular injection in rats. Under the guidance of ultrasound imaging, it is visible to find the position and observe the gray values change of nanobubbles. Thus, when triggered by focused ultrasound, the amount of insulin could be accurately pulsatile released from nanobubbles. In vivo experiments in rats showed that the visually controlled pulsatile release of insulin could be achieved for a long time, up to 3 consecutive days. The blood glucose level could be repeatedly reduced by focused ultrasound irradiation with just one injection. Our research provided a promising way for visually controlled pulsatile release of insulin, which would significantly reduce the injection frequency of insulin.

Wireless Power Transmission for Implantable Medical Devices Using Focused Ultrasound and a Miniaturized 1-3 Piezoelectric Composite Receiving Transducer.

Wireless power transmission (WPT) using ultrasound is a promising way for wirelessly recharging implantable medical devices (IMDs). However, the transmitted power using ultrasound so far is insufficient for driving the existing IMDs. Moreover, the size of the receiving transducer is larger, which is not suitable for implantation. To increase the output power and reduce the size of the implantable receiver, this article presents a method of combining focused ultrasound with a miniaturized 1-3 piezoelectric composite receiving transducer to produce higher electrical power. An analytical fluid-structure interaction model is constructed to fully understand the operating mechanism of the receiving transducer under ultrasonic force. In our experiments, a miniaturized 1-3 piezoelectric composite receiving transducer with a diameter of 3.7 mm was used. The output power generated from the receiving transducer reached 60 mW at a distance of 150 mm. In vitro and in vivo animal experiments proved that the miniaturized transducer could successfully receive focused ultrasonic energy and convert it to electrical power. The method presented and the electrical power that we obtained can provide a valuable reference for wirelessly charging of IMDs.