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Mechanochemical-induced swelling–activation of a gastric-deployable 4D-printed polypill inspired by natural hygromorphic actuators

Mechanochemical-induced swelling–activation of a gastric-deployable 4D-printed polypill inspired by natural hygromorphic actuators
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 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.

4D printings, biomimetics, gastroretentions, mechanochemical deployments, sustained drug releases, swelling activations
2640-4567
Chachlioutaki, Konstantina
aa15e449-9ebc-4a23-a5a3-4a0a1327fc8e
Papas, Nikolaos
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Chatzis, Zisis
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Katsamenis, Orestis L.
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Robinson, Stephanie K.
54d6d85c-defb-4fb6-8e78-dd82b850908c
Tsongas, Konstantinos
fecf477a-84e6-454b-8bd3-9d645d60f2c6
Bouropoulos, Nikolaos
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Fatouros, Dimitrios G.
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Tzetzis, Dimitrios
3b55f4b1-0bcc-4237-b1ba-3108c42fc6c9
Karavasili, Christina
f174d197-8ba7-4765-adc8-99fa2f1c86fa
Chachlioutaki, Konstantina
aa15e449-9ebc-4a23-a5a3-4a0a1327fc8e
Papas, Nikolaos
95363da8-ec4d-449c-b94a-5a9d694e1624
Chatzis, Zisis
e7bd344c-e8d6-4048-b712-2f6bd40a9192
Katsamenis, Orestis L.
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Robinson, Stephanie K.
54d6d85c-defb-4fb6-8e78-dd82b850908c
Tsongas, Konstantinos
fecf477a-84e6-454b-8bd3-9d645d60f2c6
Bouropoulos, Nikolaos
fadadea1-2aa2-4cd9-a7e5-33ba790cd45f
Fatouros, Dimitrios G.
c7a4f13c-3e06-4143-ae1b-8a1c0eb186cc
Tzetzis, Dimitrios
3b55f4b1-0bcc-4237-b1ba-3108c42fc6c9
Karavasili, Christina
f174d197-8ba7-4765-adc8-99fa2f1c86fa

Chachlioutaki, Konstantina, Papas, Nikolaos, Chatzis, Zisis, Katsamenis, Orestis L., Robinson, Stephanie K., Tsongas, Konstantinos, Bouropoulos, Nikolaos, Fatouros, Dimitrios G., Tzetzis, Dimitrios and Karavasili, Christina (2024) Mechanochemical-induced swelling–activation of a gastric-deployable 4D-printed polypill inspired by natural hygromorphic actuators. Advanced Intelligent Systems, [2400526]. (doi:10.1002/aisy.202400526).

Record type: Article

Abstract

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.

Text
Advanced Intelligent Systems - 2024 - Chachlioutaki - Mechanochemical‐Induced Swelling Activation of a Gastric‐Deployable - Version of Record
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e-pub ahead of print date: 20 November 2024
Keywords: 4D printings, biomimetics, gastroretentions, mechanochemical deployments, sustained drug releases, swelling activations

Identifiers

Local EPrints ID: 496923
URI: http://eprints.soton.ac.uk/id/eprint/496923
ISSN: 2640-4567
PURE UUID: 3af48538-dc40-418b-896f-0006b84d373a
ORCID for Orestis L. Katsamenis: ORCID iD orcid.org/0000-0003-4367-4147
ORCID for Stephanie K. Robinson: ORCID iD orcid.org/0000-0001-5436-2929

Catalogue record

Date deposited: 08 Jan 2025 12:58
Last modified: 17 Sep 2025 02:10

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Contributors

Author: Konstantina Chachlioutaki
Author: Nikolaos Papas
Author: Zisis Chatzis
Author: Stephanie K. Robinson ORCID iD
Author: Konstantinos Tsongas
Author: Nikolaos Bouropoulos
Author: Dimitrios G. Fatouros
Author: Dimitrios Tzetzis
Author: Christina Karavasili

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