Passive Drug Delivery Monitoring via Intra Body Communication

The concept of ingestible electronics (IE) easily enthralls our minds, picturing us in the <i>Fantastic Voyage</i> of Isaac Asimov. However, IE is supporting medicine as far back as 1957 when the first pH-endoradiosonde was presented [1]. Indeed, nowadays the research has a chance to move from ingestible to edible electronics to develop environmentally friendly, cost-effective, safe, and self-administrable edible devices [2, 3]. This transformation requires the introduction of new materials coming from food and food derivatives and/or approved by FDA/EFSA (Food and drug administration /European food safety authority) enabling a new healthcare platform. One of the most attractive visions and expectations from edible electronics is the development of an edible device for monitoring all the pharmacological therapy in chronic and thorny diseases. Such technology is prevented in ingestible electronic systems because of cost, security, and ethical issues[4].<br/>For many pathologies, precise and sustained pharmacological therapy is crucial for disease control and/or recovery[5]. Such administration/management is obtained by two main approaches, a correct pharmacological adherence [6] together with the use of controlled drug release system/technology[7]. One of the main bottlenecks in the development of such devices is a proper sensing and communication system compatible with edible electronic state of the art Indeed, common wireless communication platforms such as Bluetooth, Zigbee, or Wi-Fi require complicated logic circuits (CMOS technology), low impedance conductors for antennas implementation, and relatively high power density (hundreds nJ/bit) not replaceable with edible components [8]. In this context, the most promising communication strategy is the Intra Body Communication (IBC) introduced by Zimmerman in 1996 [9]. IBC is a wireless bio inspired communication platform that exploits the body's ionic conductivity to propagate a signal (e.e. nervous system), generating a wireless body area network.<br/>Here we present a technology that will enable the monitor of both, pharmacological adherence and real-time drug release. The presented proof of concept (POC), realized starting from food grade and food additives materials, exploits a passive intrabody communication (IBC) modulation triggered by the material degradation and resulting drug release in the gastrointestinal tract. The POC has been designed for the metformin intestinal targeted release detection and monitoring. The system showed a Limit of Cumulative Drug Release Detection of 19 μg/ml and a Limit of Real-Time Drug Release Detection of 2 μg/ml*min.<br/>1. Jacobson, B. and R.S. Mackay, <i>A pH-endoradiosonde.</i> The Lancet, 1957. <b>269</b>(6981): p. 1224.<br/>2. Sharova, A.S., et al., <i>Edible electronics: The vision and the challenge.</i> Advanced Materials Technologies, 2021. <b>6</b>(2): p. 2000757.<br/>3. Bonacchini, G.E., et al., <i>Tattoo Paper Transfer as a Versatile Platform for All Printed Organic Edible Electronics.</i> Advanced Materials, 2018. <b>30</b>(14): p. 1706091.<br/>4. Gerke, S., et al., <i>Ethical and legal issues of ingestible electronic sensors.</i> Nature Electronics, 2019. <b>2</b>(8): p. 329-334.<br/>5. Kang, J.-S. and M.-H. Lee, <i>Overview of therapeutic drug monitoring.</i> The Korean journal of internal medicine, 2009. <b>24</b>(1): p. 1.<br/>6. Lerman, I., <i>Adherence to treatment: the key for avoiding long-term complications of diabetes.</i> Archives of medical research, 2005. <b>36</b>(3): p. 300-306.<br/>7. Rosen, H. and T. Abribat, <i>The rise and rise of drug delivery.</i> Nature Reviews Drug Discovery, 2005. <b>4</b>(5): p. 381-385.<br/>8. Chen, C.-A., et al., <i>VLSI implementation of an efficient lossless EEG compression design for wireless body area network.</i> Applied Sciences, 2018. <b>8</b>(9): p. 1474.<br/>9. Zimmerman, T.G., <i>Personal area networks: Near-field intrabody communication.</i> IBM systems Journal, 1996. <b>35</b>(3.4): p. 609-617.