Therapeutic luminal coating of the intestine
Authors: Yuhan Lee, Tara E. Deelman, Keyue Chen, Dawn S. Y. Lin, Ali Tavakkoli, Jeffrey M. Karp
Summary:
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: Nature Materials, 2018
Summary:
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: Nature Materials, 2018