School of Life Sciences, The University of Dundee, Dundee, DD1 5EH, UK.
Department of Electronic and Electrical Engineering, The University of Strathclyde, Glasgow, G1 1XQ, UK.
Sci Rep. 2021 Jan 28;11(1):2584. doi: 10.1038/s41598-021-82240-1.
Biologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focused ultrasound during in vivo experiments using porcine models. This study illustrates how such a device could be potentially used for gastrointestinal drug delivery and the challenges to be overcome before focused ultrasound and microbubbles could be used with this device for the oral delivery of biologic therapeutics.
生物药物被定义为从生物体中产生或含有成分的治疗剂，对制药行业越来越重要。虽然口服给药很方便，但由于生物制剂通过口服途径的生物利用度较差，因此需要进行侵入性注射。使用类似于胶囊内窥镜的电子输送装置将生物制剂输送到小肠是克服这一限制的一种很有前途的方法，而且不需要对治疗剂进行重新配方。通过在肠道衬里中集成超声换能器来增加通透性来提高这种胶囊装置的药物输送效果，可以进一步提高其功效。本文介绍了一种新型的概念验证胶囊装置，该装置能够进行电子应用的聚焦超声和治疗剂的输送。荧光标记物被选为模型药物，用于证明在猪小肠中的体内输送。我们展示了在使用猪模型的体内实验中，当将微泡与聚焦超声结合使用时，低声功率可以使荧光标记物穿透小肠的粘液层。这项研究说明了这种装置如何可用于胃肠道药物输送，以及在聚焦超声和微泡可用于该装置进行生物治疗的口服输送之前需要克服的挑战。
