Hind Al-Haddad, Daniele Guarnera, Izadyar Tamadon, Lorenzo Arrico, Giulia Ballardini, Francesco Mariottini, Alessio Cucini, Simone Ricciardi, Fabio Vistoli, Maria Isabella Rotondo, Daniela Campani, Xuyang Ren, Gastone Ciuti, Benjamin Terry, Veronica Iacovacci, Leonardo Ricotti
{"title":"用于植入式设备非侵入性填充的优化磁性对接可吞食胶囊","authors":"Hind Al-Haddad, Daniele Guarnera, Izadyar Tamadon, Lorenzo Arrico, Giulia Ballardini, Francesco Mariottini, Alessio Cucini, Simone Ricciardi, Fabio Vistoli, Maria Isabella Rotondo, Daniela Campani, Xuyang Ren, Gastone Ciuti, Benjamin Terry, Veronica Iacovacci, Leonardo Ricotti","doi":"10.1002/aisy.202400125","DOIUrl":null,"url":null,"abstract":"<p>Automated drug delivery systems (ADDS) improve chronic disease management by enhancing adherence and reducing patient burden, particularly in conditions like type 1 diabetes, through intraperitoneal insulin delivery. However, periodic invasive refilling of the reservoir is needed in such a class of implantable devices. In previous work, an implantable ADDS with a capsule docking system is introduced for non-invasive reservoir refilling. Yet, it encounters reliability issues in manufacturing, sealing, and docking design and lacks evidence on intestinal tissue compression effects and chronic in vivo data. This work proposes an optimization of the different components featuring this ADDS. The ingestible capsule is designed, developed, and tested following ISO 13485, exhibiting high insulin stability and optimal sealing for six days in harsh gastrointestinal-like conditions. A magnetic docking system is optimized, ensuring reliable and stable capsule docking at a clinically relevant distance of 5.92 mm. Histological tests on human intestinal tissues confirm safe capsule compression during docking. Bench tests demonstrate that the integrated mechatronic system effectively docks capsules at various peristalsis-mimicking velocities. A six-week in vivo test on porcine models demonstrates chronic safety and provides hints on fibrotic reactions. These results pave the way for the further evolution of implantable ADDS.</p>","PeriodicalId":93858,"journal":{"name":"Advanced intelligent systems (Weinheim an der Bergstrasse, Germany)","volume":"6 11","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aisy.202400125","citationCount":"0","resultStr":"{\"title\":\"Optimized Magnetically Docked Ingestible Capsules for Non-Invasive Refilling of Implantable Devices\",\"authors\":\"Hind Al-Haddad, Daniele Guarnera, Izadyar Tamadon, Lorenzo Arrico, Giulia Ballardini, Francesco Mariottini, Alessio Cucini, Simone Ricciardi, Fabio Vistoli, Maria Isabella Rotondo, Daniela Campani, Xuyang Ren, Gastone Ciuti, Benjamin Terry, Veronica Iacovacci, Leonardo Ricotti\",\"doi\":\"10.1002/aisy.202400125\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Automated drug delivery systems (ADDS) improve chronic disease management by enhancing adherence and reducing patient burden, particularly in conditions like type 1 diabetes, through intraperitoneal insulin delivery. However, periodic invasive refilling of the reservoir is needed in such a class of implantable devices. In previous work, an implantable ADDS with a capsule docking system is introduced for non-invasive reservoir refilling. Yet, it encounters reliability issues in manufacturing, sealing, and docking design and lacks evidence on intestinal tissue compression effects and chronic in vivo data. This work proposes an optimization of the different components featuring this ADDS. The ingestible capsule is designed, developed, and tested following ISO 13485, exhibiting high insulin stability and optimal sealing for six days in harsh gastrointestinal-like conditions. A magnetic docking system is optimized, ensuring reliable and stable capsule docking at a clinically relevant distance of 5.92 mm. Histological tests on human intestinal tissues confirm safe capsule compression during docking. Bench tests demonstrate that the integrated mechatronic system effectively docks capsules at various peristalsis-mimicking velocities. A six-week in vivo test on porcine models demonstrates chronic safety and provides hints on fibrotic reactions. These results pave the way for the further evolution of implantable ADDS.</p>\",\"PeriodicalId\":93858,\"journal\":{\"name\":\"Advanced intelligent systems (Weinheim an der Bergstrasse, Germany)\",\"volume\":\"6 11\",\"pages\":\"\"},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aisy.202400125\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced intelligent systems (Weinheim an der Bergstrasse, Germany)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/aisy.202400125\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"AUTOMATION & CONTROL SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced intelligent systems (Weinheim an der Bergstrasse, Germany)","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/aisy.202400125","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"AUTOMATION & CONTROL SYSTEMS","Score":null,"Total":0}
Optimized Magnetically Docked Ingestible Capsules for Non-Invasive Refilling of Implantable Devices
Automated drug delivery systems (ADDS) improve chronic disease management by enhancing adherence and reducing patient burden, particularly in conditions like type 1 diabetes, through intraperitoneal insulin delivery. However, periodic invasive refilling of the reservoir is needed in such a class of implantable devices. In previous work, an implantable ADDS with a capsule docking system is introduced for non-invasive reservoir refilling. Yet, it encounters reliability issues in manufacturing, sealing, and docking design and lacks evidence on intestinal tissue compression effects and chronic in vivo data. This work proposes an optimization of the different components featuring this ADDS. The ingestible capsule is designed, developed, and tested following ISO 13485, exhibiting high insulin stability and optimal sealing for six days in harsh gastrointestinal-like conditions. A magnetic docking system is optimized, ensuring reliable and stable capsule docking at a clinically relevant distance of 5.92 mm. Histological tests on human intestinal tissues confirm safe capsule compression during docking. Bench tests demonstrate that the integrated mechatronic system effectively docks capsules at various peristalsis-mimicking velocities. A six-week in vivo test on porcine models demonstrates chronic safety and provides hints on fibrotic reactions. These results pave the way for the further evolution of implantable ADDS.