A swallowable smart pill for drug delivery into the gastrointestinal tract

Gastrointestinal system diseases are the most common cause of mortality and hospitalization (21.7 million 2010 in USA (2010)) in developed countries and, due to demographic changes, are still on the rise. Different pathologies are specific for every tract of the gastrointestinal system, from the esophagus to the bowel. In particular, chronic inflammatory diseases are widespread and require long lasting therapies. A new frontier in treatment of chronic diseases is represented by localized therapies that can bring benefits in terms of quantity of medication delivered and costs of the treatment. In recent years technologies in medical robotics and micromechatronics are steadily growing and are capable of producing safe enough solutions to be applied in medicine. In fact, it is possible to find robots that help in several subdomains such as surgery, diagnosis and therapy. In addition, the development of Micro-Electro-Mechanical Systems (MEMS) technology permits the miniaturization of robots to use them in a less invasive way. In particular, untethered endoscopic tools have been developed and commercialized in order to reduce discomfort to the patients. To date, it has been shown that endoscopic capsules can provide more cost effective solutions than wired endoscopes for the same performance. As an example, capsule endoscopes overcome problems of insertion and intubation. Furthermore, capsules can navigate deeply into the small intestine, that usually is a dead zone for wired endoscopes. Despite capsule endoscopes are widespread, new tools are to be developed for drug delivery and biopsy in order to implement therapeutic and intervention properties on the capsule. Focusing on therapeutic properties, capsules for drug delivery provide the possibility to improve the treatment of chronic gastrointestinal diseases. Major advantages that the use of capsule for drug delivery can bring are i) localized therapy, with a consequent reduction of drug doses and reduced side effects compared to systemic administration, ii) costs reduction, thanks to significantly reduced drug doses and iii) shortened hospitalization periods for patients. These advantages confer to capsules for therapeutic action a dominant role in new medical treatments, in particular for local drug delivery. The aim of this thesis is to investigate how to develop an autonomous micromechatronic system and how therapeutic functionalities can be embedded on a swallowable capsule. To this aim the following main topics have been addressed: 1. Design and fabrication of an autonomous smart pill, considering environmental requirements and biocompatibility. 2. Integration of micro-electronics on-board for autonomous navigation and sensors to monitor physiological conditions of the gastrointestinal tract and trigger the activation of the drug delivery system. 3. Development of an active drug delivery system to be integrated on a swallowable capsule. To these purposes special attention has been given to: - the environment requirements in term of size, materials biocompatibility and power supply. - The development of a sensing system capable of triggering the activation of the drug delivery system. - The development of an effective drug delivery system capable of delivering a controlled desired amount of drug thanks to a custom made drug delivery pump sensorized with a novel strain sensor. In the thesis micromechatronics design principles and their specific application to medicine are detailed together with features of smart pills. Analyzing the state of the art, requirements and open challenges in the field of smart pills are pointed out, so the architecture of the system developed and the design of the capsule is described considering biocompatibility and size issues (topic 1). Then the sensing system (topic 2) is described. The use of impedance measurement in medical practice and the advantages of using impedance as a medical index for pathological alterations of gastrointestinal tissue properties are explored. The developed of the impedance sensor is then tested and results are presented. Then the development of the drug delivery system (topic 3) is presented. The design and fabrication of the custom made drug delivery system are presented together with its performances. As for local drug delivery a volume of 50 µl is required, a custom made electrolytic micro pump has been designed and integrated on board. The pump for drug release is sensorized with a novel strain sensor and different solutions for the sensorization are presented and discussed. The sensorization of the membrane is functional to the control of the volume of drug released. One major advantage of the use of a strain sensor is the resulting versatility of the system: the smart pill can be used to deliver different types of drugs, not being influenced by the viscosity of the medication, neither by external conditions (e.g. gastric fluids pressure). Finally, a swallowable smart pill has been designed and developed, its sensor system for lesion localization has been developed and tested and a novel drug delivery system, a novel drug delivery system has been developed and sensorized for the monitoring of the drug released.