Therapeutic luminal coating of the intestine

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.

Biomimetic intestinal barrier based on microfluidic encapsulated sucralfate microcapsules

“…CT imaging and IVIS were used to visualize the biomimetic intestinal barrier on the gut surface in vivo [14]. In CT imaging, sucralfate was composed with diodone and encapsulated in microcapsules for gavage.…”

“…1. Benefiting from their capability to separate liquid cargo and solid encapsulant as well as high cargo content, microcapsules have been widely applied in encapsulation, delivery, and release of actives in the fields of agriculture, cosmetics, drug delivery, detergents, and food additives [14][15][16][17][18]. A variety of techniques, such as spray drying, interfacial polymerization, complex coacervation, and microfluidics, have been employed for the preparation of functional microcapsules [19][20][21][22][23][24][25][26].…”

Real-time manipulation of intestinal peristalsis by enteric-encapsulated magnetic nanoparticles & wearable 3D-printed devices

“…In addition, group C (fed with high-fat food & H-field) and group D (fed with high-fat food & E-capsules) presented a relatively low absorption of xylose. This result was due to the presence of hydrophilic methylcellulose, the main component of the capsule, which could adsorb small water-soluble molecules and reduce absorption through the small intestine 29 . This result also indicated that the method could effectively decrease the absorption of water-soluble substances but would not form an effective barrier for fat-soluble substances.…”

Gastrointestinal synthetic epithelial linings

“…Another essential function of the small intestine is regulation of plasma glucose concentrations, which are frequently associated with metabolic disorders and systemic diseases, such as obesity, hyperinsulinemia, and diabetes mellitus (36). To modulate nutrient absorption in patients with these disorders, treatments such as gastric bypass surgery, intestinal sleeve placement, intestinal mucosal resurfacing, surgical adhesives, and GI electrical stimulation have been applied (5,6,8,37,38). However, these procedures can be invasive and manifest with adverse effects.…”