journal article·2018-09

Therapeutic luminal coating of the intestine

Yuhan Lee, Tara E. Deelman, Keyue Chen, Dawn S. Y. Lin, Ali Tavakkoli, Jeffrey M. Karp

Nature Materials· Volume 17· Issue 9
Publisher page

Abstract

The gastrointestinal tract is the site of most drug delivery and therapeutic interventions for the management and treatment of numerous diseases. However, selective access to its mucosa, especially in the small bowel, is challenging. Here we develop an orally administered gut-coating formulation that provides a transient coating of the bowel. Through a materials screening campaign, we identified a sucrose octasulfate aluminium complex and further engineered the pH-dependent material into a complex coacervate formulation linked via pH-independent electrostatic interaction, which allowed an effective transient physical coating on the gastrointestinal mucosa, independent of gastric acid exposure. We tested the therapeutic values of this technology in two settings. Oral administration of this gut-coating formulation modulated the nutrient contact with bowel mucosa, which lowered the glucose responses in rodent models indicating a potential therapeutic utility in diabetes. Furthermore, the formulation protected biological agents from gastric acid exposure and degradation, which enabled oral delivery to the small bowel mucosa.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Gastrointestinal motility and disorders · Diabetes Treatment and Management · Helicobacter pylori-related gastroenterology studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (25)

Show source-provided references
1. American Diabetes Association 2 Classification and diagnosis of diabetes. Diabetes Care 39 S13–S22; erratum. Diabetes Care 39, 1653 (2016).10.2337/dc16-er09 ↗
2. Mingrone, G. et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N. Engl. J. Med 366, 1577–1585 (2012).10.1056/NEJMoa1200111 ↗
3. Lovshin, J. A. & Drucker, D. J. Incretin-based therapies for type 2 diabetes mellitus.Nat. Rev. Endocrinol. 5, 262–269 (2009).10.1038/nrendo.2009.48 ↗
4. Drucker, D. J. & Nauck, M. A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368, 1696–1705 (2006).10.1016/S0140-6736(06)69705-5 ↗
5. Stefater, M. A., Wilson-Pérez, H. E., Chambers, A. P., Sandoval, D. A. & Seeley, R. J. All bariatric surgeries are not created equal: insights from mechanistic comparisons. Endocr. Rev. 33, 595–622 (2012).10.1210/er.2011-1044 ↗
6. Rubino, F. et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann. Surg. 240, 236–242 (2004).10.1097/01.sla.0000133117.12646.48 ↗
7. Jorgensen, N. B. et al. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance. Am. J. Physiol. Endocrinol. Metab. 303, E122–E131 (2012).10.1152/ajpendo.00073.2012 ↗
8. Zhang, S., Bellinger, A. M., Glettig, D. L. & Barman, R. A pH-responsive supramolecular polymer gel as an enteric elastomer for use in gastric devices. Nat. Mater. 14, 1065–1073 (2015).10.1038/nmat4355 ↗
9. Zelikin, A. N., Ehrhardt, C. & Healy, A. M. Materials and methods for delivery of biological drugs. Nat. Chem. 8, 997–1007 (2016).10.1038/nchem.2629 ↗
10. Fuhrmann, G. Sustained gastrointestinal activity of dendronized polymer–enzyme conjugates. Nat. Chem. 5, 582–589 (2013).10.1038/nchem.1675 ↗
11. Danesh, B. J., Duncan, A. & Russell, R. I. Is an acid pH medium required for the protective effect of sucralfate against mucosal injury? Am. J. Med. 83, 11–13 (1987).10.1016/0002-9343(87)90820-5 ↗
12. Morris, G. P. (eds D. Hollander & G. Tytgat) Sucralfate: From Basic Science to the Bedside. 71–82 (Springer, New York, NY, 1995).
13. Nagashima, R. Mechanisms of action of sucralfate. J. Clin. Gastroenterol. 3, 117–127 (1981).
14. Ochi, K. (eds D. Hollander & G. Tytgat) Sucralfate: From Basic Science to the Bedside. 47–58 (Springer, New York, NY, 1995).10.1007/978-0-585-32154-7_5 ↗
15. McCarthy, D. M. Drug therapy: sucralfate. New Engl. J. Med. 325, 1017–1025 (1991).10.1056/NEJM199110033251407 ↗
16. Nail, S. L., White, J. L. & Hem, S. L. Structure of aluminum hydroxide gel. I: Initial precipitate. J. Pharm. Sci. 65, 1188–1191 (1976).10.1002/jps.2600650814 ↗
17. Hem, J. D. & Roberson, C. E. Form and Stability of Aluminum Hydroxide Complexes in Dilute Solution Water Supply Paper 1827-A (Geological Survey, Washington DC, 1967).
18. Wang, Q. & Schlenoff, J. B. The polyelectrolyte complex/coacervate continuum. Macromolecules 47, 3108–3116 (2014).10.1021/ma500500q ↗
19. de Kruif, C. G., Weinbreck, F. & de Vries, R. Complex coacervation of proteins and anionic polysaccharides. Curr. Opin. Colloid Interface Sci. 9, 340–349 (2004).10.1016/j.cocis.2004.09.006 ↗
20. Veis, A. & Aranyi, C. Phase separation in polyelectrolyte systems. I. Complex coacervates of gelatin. J. Phys. Chem. 64, 1203–1210 (1960).10.1021/j100838a022 ↗
21. Cummings, D. E. & Flum, D. R. Gastrointestinal surgery as a treatment for diabetes. J. Am. Med. Assoc. 299, 341–343 (2008).
22. Couzin, J. Bypassing medicine to treat diabetes. Science 320, 438–440 (2008).10.1126/science.320.5875.438 ↗
23. Betzel, B. et al. Weight reduction and improvement in diabetes by the duodenal–jejunal bypass liner: a 198 patient cohort study. Surg. Endosc. 31, 2881–2891 (2016).10.1007/s00464-016-5299-6 ↗
24. Koehestanie, P. et al. Duodenal–jejunal bypass liner implantation provokes rapid weight loss and improved glycemic control, accompanied by elevated fasting ghrelin levels. Endosc. Int. Open 2, E21–E27 (2014).10.1055/s-0034-1365222 ↗
25. Cohen, R. et al. Role of proximal gut exclusion from food on glucose homeostasis in patients with Type 2 diabetes. Diabetes Med. 30, 1482–1486 (2013).10.1111/dme.12268 ↗