Excess nutrient uptake is one of the main factors of complications related to metabolism disorders. Therefore, efforts have emerged to modulate nutrient transport in the intestine. However, current approaches are mainly invasive interventions with various side effects. Here, a pH-responsive hydrogel is formulated by acidifying the hydroxide compounds within sucralfate to allow electrostatic interactions between pectin and aluminum ions. The pH responsiveness relies on the alternation of cations and hydroxide species, providing reversible shifting from a hydrogel to a complex coacervate system. It acts as a transient physical barrier coating to inhibit intestinal absorption and changes the viscosity and barrier function in different parts of the gastrointestinal tract, showing enhanced mucoadhesive properties. The therapeutic hydrogel remarkably lowers the immediate blood glucose response by modulating nutrient contact with bowel mucosa, suggesting potential in treating diabetes. In addition, it significantly reduces weight gain, fat accumulation, and hepatic lipid deposition in rodent models. This study provides a novel strategy for fabricating pH-responsive hydrogels, which may serve as a competent candidate for metabolism disorder management.

Obesity is characterized as abnormal or excessive fat accumulation harmful to one’s health, linked to hormonal imbalances, cardiovascular illness, and coronary artery disease. Since the disease stems mainly from overconsumption, studies have aimed to control intestinal absorption as a route for treatment. In this study, chitosan-thioglycolic acid (CT) was developed as a physical barrier in the gastrointestinal tracts to inhibit nutrient uptake. CT exhibits a superior mucoadhesive property compared to chitosan both in vitro and in vivo for the ability to form disulfide bonds with the intestinal mucosa. For CT as a potential drug delivery platform, hesperidin, a herb for bodyweight control in traditional Chinese medication, is encapsulated in CT and can be released consistently from this absorption barrier. In animal studies, CT encapsulated with hesperidin (CTH) not only results in a weight-controlling effect but limits adipose accumulation by hindering absorption, suggesting a potential role in obesity treatment. Neither CT nor CTH exhibit cytotoxicity or produce adverse immunological reactions in vivo.

Nowadays, nonalcoholic fatty liver disease is a common metabolic liver disease of all ages worldwide. However, current pharmacological and surgical treatments are accompanied with side effects and complications. EndoBarrier, a less invasive bariatric surgery, blocks the upper portion of the intestine to reduce nutrition absorption. To mimic the nutrient restriction effect of EndoBarrier, thiol-containing materials may bind to the thiol groups of the mucus with an enhanced mucoadhesive property. Here, we develop thiolated alginate with cysteine conjugation via an N-(3-dimethylaminopropyl)-N-ethylcarbodiimide/N-hydroxysuccinimide reaction. The alginate–cysteine (AC) exhibits excellent mucoadhesive properties and forms a physical barrier in the intestine to reduce absorption significantly, which was tested with both in vitro and in vivo mucoadhesive test and barrier function test. The nontoxicity property of AC was also proven with WST-1 and live and dead stain. In addition, AC demonstrates potent carrier properties of extending the release of resveratrol to improve the efficacy with the test of the transwell system in the release profile. In the long-term therapeutic evaluation, alginate cysteine with resveratrol (ACR) is orally administrated daily to mice with an methionine choline-deficient diet. The results of this in vivo study show that developed ACR could effectively alleviate fat degeneration in the liver and improve fat-related metabolic parameters in serum without hepatocellular damage and kidney dysfunction. In sum, AC was found to be mucoadhesive, reduce glucose absorption, alleviate inflammation, and decrease fatty degradation. This promising material exhibits the potential to be a supplement for nonalcoholic fatty liver disease.

Obesity is the most common health concern all over the world. However, till now, there is no promising way to manage obesity or body‐weight control. The aim of the study is to develop an edible gel as a health supplement that temporarily attaches to the mucus of the intestines, forming an absorption barrier to block the nutrients. We modify the alginate with the thiol group as thiolated alginate (TA) that may stay on the mucosa layer for a much longer time to reduce nutrient absorption. In this study, the TA is synthesized successfully and proved a good mucosal adhesion to serve as a barrier for nutrient absorption both in vitro and in vivo. The results of in vivo imaging system (IVIS) show that the synthesized TA can be exiled from the gastrointestinal tract within 24 h. The animal study shows that the TA by daily oral administration can effectively reduce body weight and fat deposition. The biosafety is evaluated in vitro at the cellular level, based on ISO‐10993, and further checked by animal study. We do believe that the TA could have a greater potential to be developed into a safe health supplement to manage obesity and for body‐weight control.

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