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A pH-responsive supramolecular polymer gel as an enteric elastomer for use in gastric devices

Abstract

Devices resident in the stomach—used for a variety of clinical applications including nutritional modulation for bariatrics, ingestible electronics for diagnosis and monitoring, and gastric-retentive dosage forms for prolonged drug delivery—typically incorporate elastic polymers to compress the devices during delivery through the oesophagus and other narrow orifices in the digestive system. However, in the event of accidental device fracture or migration, the non-degradable nature of these materials risks intestinal obstruction. Here, we show that an elastic, pH-responsive supramolecular gel remains stable and elastic in the acidic environment of the stomach but can be dissolved in the neutral-pH environment of the small and large intestines. In a large animal model, prototype devices with these materials as the key component demonstrated prolonged gastric retention and safe passage. These enteric elastomers should increase the safety profile for a wide range of gastric-retentive devices.

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Figure 1: Schematic representation, manufacturing and macroscopic characteristics of the enteric elastomer.
Figure 2: Physical characterization of the enteric elastomer.
Figure 3: Construction of a ring-shaped gastric-retentive device and in vitro testing of its elasticity and enteric property.
Figure 4: In vivo evaluation of the ring-shaped devices in Yorkshire pigs.
Figure 5: In vivo evaluation of M-shaped (30 mm × 30 mm × 4 mm), I-shaped (30 mm × 18 mm × 4 mm) and T-shaped (30 mm × 18 mm × 4 mm) devices.

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Acknowledgements

This work was funded in part by the Bill and Melinda Gates Foundation Grant OPP1096734 (to R.L.) and the NIH Grant EB000244 (to R.L.). The paper was partly sponsored by the Alexander von Humboldt Foundation under the auspices of the Max Planck Research Award to R.L. funded by the Federal Ministry of Education and Research. A.M.B. was supported in part by NIH T32 5T32HL007604-29. J.Z. was supported by the Laboratory Directed Research and Development program at Oak Ridge National Laboratory, which is sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy. Use of the Advanced Photon Source, an Office of Science User Facility operated for the US Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the US DOE under Contract No. DE-AC02-06CH11357. We would like to thank J. Haupt and M. Jamiel for expert veterinary support. We are indebted to L. Wood, P. Eckhoff, D. Hartman, S. Kern, S. Hershenson and B. Nikolic for fruitful discussions that stimulated the development of this material. The findings and conclusions reported in this paper are those of the authors and do not necessarily reflect positions or policies of the Bill and Melinda Gates Foundation.

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Authors

Contributions

S.Z., R.L. and G.T. designed the material and experiments. S.Z. prepared the material and the device. S.Z., A.M.B., D.L.G., R.B., Y.-A.L.L., J.Z., V.A.M., C.C., L.D.N., D.J.M., L.G. and G.T. characterized the material, analysed the data and wrote the paper. R.L. and G.T. supervised the research. All authors discussed the progress of research and reviewed the manuscript.

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Correspondence to Robert Langer or Giovanni Traverso.

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The authors declare Provisional US patent application No. 62/010,992 filed on 11 June 2014.

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Zhang, S., Bellinger, A., Glettig, D. et al. A pH-responsive supramolecular polymer gel as an enteric elastomer for use in gastric devices. Nature Mater 14, 1065–1071 (2015). https://doi.org/10.1038/nmat4355

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