Mechanochemical‐Induced Swelling–Activation of a Gastric‐Deployable 4D‐Printed Polypill Inspired by Natural Hygromorphic Actuators
Gastroretentive drug delivery systems can improve adherence in patients with chronic diseases (CDs), but current options lack dose flexibility and involve complex fabrication methods. Inspired by the hygroscopic deformation observed in multilayered pine cone scales, wherein hydration of the outer ac...
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| Format: | Article |
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Wiley
2025-04-01
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| Series: | Advanced Intelligent Systems |
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| Online Access: | https://doi.org/10.1002/aisy.202400526 |
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| author | Konstantina Chachlioutaki Nikolaos Papas Zisis Chatzis Orestis L. Katsamenis Stephanie K. Robinson Konstantinos Tsongas Nikolaos Bouropoulos Dimitrios G. Fatouros Dimitrios Tzetzis Christina Karavasili |
| author_facet | Konstantina Chachlioutaki Nikolaos Papas Zisis Chatzis Orestis L. Katsamenis Stephanie K. Robinson Konstantinos Tsongas Nikolaos Bouropoulos Dimitrios G. Fatouros Dimitrios Tzetzis Christina Karavasili |
| author_sort | Konstantina Chachlioutaki |
| collection | DOAJ |
| description | Gastroretentive drug delivery systems can improve adherence in patients with chronic diseases (CDs), but current options lack dose flexibility and involve complex fabrication methods. Inspired by the hygroscopic deformation observed in multilayered pine cone scales, wherein hydration of the outer active layer induces cone closure, a one‐step fabrication method of a personalized 4D‐printed water‐actuated four‐arm polypill is demonstrated in this study. The bilayer‐arm polypill self‐deploys upon ingestion to prolong gastric retention and sustain drug release. By inversing the orientation of the swellable active layer at the polypill arms compared to pine cone scales, a differential swelling strain develops generating bending force that enables polypill deployment to constrain passage through the pylorus. Finite‐element analysis is used to model spatial changes in polymer phase swelling to ensure adequate deployment within the timeframe of gastric emptying. In a stomach model, the polypill expanded to 30 mm over 2 h, exceeding the diameter of the stomach model's distal end. In an in vitro release screening, biocompatible polymer composites capable of providing up to 6 days of release for a three‐drug combination for tuberculosis–HIV coinfected patients are identified. The bioinspired 4D‐printed polypill can serve as drug delivery platform for a range of CDs. |
| format | Article |
| id | doaj-art-9814d88da5d14dbdbbdcfb44749603a8 |
| institution | DOAJ |
| issn | 2640-4567 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Intelligent Systems |
| spelling | doaj-art-9814d88da5d14dbdbbdcfb44749603a82025-08-20T03:08:43ZengWileyAdvanced Intelligent Systems2640-45672025-04-0174n/an/a10.1002/aisy.202400526Mechanochemical‐Induced Swelling–Activation of a Gastric‐Deployable 4D‐Printed Polypill Inspired by Natural Hygromorphic ActuatorsKonstantina Chachlioutaki0Nikolaos Papas1Zisis Chatzis2Orestis L. Katsamenis3Stephanie K. Robinson4Konstantinos Tsongas5Nikolaos Bouropoulos6Dimitrios G. Fatouros7Dimitrios Tzetzis8Christina Karavasili9Laboratory of Pharmaceutical Technology Department of Pharmacy Aristotle University of Thessaloniki Thessaloniki 54124 GreeceDigital Manufacturing and Materials Characterization Laboratory School of Science and Technology International Hellenic University Thermi 57001 GreeceLaboratory of Pharmaceutical Technology Department of Pharmacy Aristotle University of Thessaloniki Thessaloniki 54124 Greeceμ‐VIS X‐Ray Imaging Centre Faculty of Engineering and Physical Sciences University of Southampton University road Highfield campus Southampton SO17 1BJ UKμ‐VIS X‐Ray Imaging Centre Faculty of Engineering and Physical Sciences University of Southampton University road Highfield campus Southampton SO17 1BJ UKDepartment of Industrial Engineering and Management School of Engineering International Hellenic University Thessaloniki 57001 GreeceDepartment of Materials Science University of Patras Patras 26504 GreeceLaboratory of Pharmaceutical Technology Department of Pharmacy Aristotle University of Thessaloniki Thessaloniki 54124 GreeceDigital Manufacturing and Materials Characterization Laboratory School of Science and Technology International Hellenic University Thermi 57001 GreeceLaboratory of Pharmaceutical Technology Department of Pharmacy Aristotle University of Thessaloniki Thessaloniki 54124 GreeceGastroretentive drug delivery systems can improve adherence in patients with chronic diseases (CDs), but current options lack dose flexibility and involve complex fabrication methods. Inspired by the hygroscopic deformation observed in multilayered pine cone scales, wherein hydration of the outer active layer induces cone closure, a one‐step fabrication method of a personalized 4D‐printed water‐actuated four‐arm polypill is demonstrated in this study. The bilayer‐arm polypill self‐deploys upon ingestion to prolong gastric retention and sustain drug release. By inversing the orientation of the swellable active layer at the polypill arms compared to pine cone scales, a differential swelling strain develops generating bending force that enables polypill deployment to constrain passage through the pylorus. Finite‐element analysis is used to model spatial changes in polymer phase swelling to ensure adequate deployment within the timeframe of gastric emptying. In a stomach model, the polypill expanded to 30 mm over 2 h, exceeding the diameter of the stomach model's distal end. In an in vitro release screening, biocompatible polymer composites capable of providing up to 6 days of release for a three‐drug combination for tuberculosis–HIV coinfected patients are identified. The bioinspired 4D‐printed polypill can serve as drug delivery platform for a range of CDs.https://doi.org/10.1002/aisy.2024005264D printingsbiomimeticsgastroretentionsmechanochemical deploymentssustained drug releasesswelling activations |
| spellingShingle | Konstantina Chachlioutaki Nikolaos Papas Zisis Chatzis Orestis L. Katsamenis Stephanie K. Robinson Konstantinos Tsongas Nikolaos Bouropoulos Dimitrios G. Fatouros Dimitrios Tzetzis Christina Karavasili Mechanochemical‐Induced Swelling–Activation of a Gastric‐Deployable 4D‐Printed Polypill Inspired by Natural Hygromorphic Actuators Advanced Intelligent Systems 4D printings biomimetics gastroretentions mechanochemical deployments sustained drug releases swelling activations |
| title | Mechanochemical‐Induced Swelling–Activation of a Gastric‐Deployable 4D‐Printed Polypill Inspired by Natural Hygromorphic Actuators |
| title_full | Mechanochemical‐Induced Swelling–Activation of a Gastric‐Deployable 4D‐Printed Polypill Inspired by Natural Hygromorphic Actuators |
| title_fullStr | Mechanochemical‐Induced Swelling–Activation of a Gastric‐Deployable 4D‐Printed Polypill Inspired by Natural Hygromorphic Actuators |
| title_full_unstemmed | Mechanochemical‐Induced Swelling–Activation of a Gastric‐Deployable 4D‐Printed Polypill Inspired by Natural Hygromorphic Actuators |
| title_short | Mechanochemical‐Induced Swelling–Activation of a Gastric‐Deployable 4D‐Printed Polypill Inspired by Natural Hygromorphic Actuators |
| title_sort | mechanochemical induced swelling activation of a gastric deployable 4d printed polypill inspired by natural hygromorphic actuators |
| topic | 4D printings biomimetics gastroretentions mechanochemical deployments sustained drug releases swelling activations |
| url | https://doi.org/10.1002/aisy.202400526 |
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