RESUMEN
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.
RESUMEN
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.
Asunto(s)
Quitosano/farmacología , Sistemas de Liberación de Medicamentos , Tracto Gastrointestinal/metabolismo , Hesperidina , Absorción Intestinal/efectos de los fármacos , Nutrientes/metabolismo , Obesidad/tratamiento farmacológico , Tioglicolatos/farmacología , Animales , Células Cultivadas , Quitosano/metabolismo , Quitosano/uso terapéutico , Disulfuros/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Masculino , Ratones Endogámicos C57BL , Tioglicolatos/metabolismo , Tioglicolatos/uso terapéuticoRESUMEN
Temozolomide (TMZ)-resistant glioblastoma multiforme (GBM) cells would have abnormal redox status due to bio-thiols, like glutathione (GSH), which constitute the most crucial defense system that protects cells from therapeutic agents. Current strategies for GSH detection often require sophisticated instruments that may not be available in laboratories with fewer resources. Here, we circumvent this problem by introducing a lateral flow plasmonic biosensor (LFPB) based on gold-viral biomineralized nanoclusters (AuVCs) as nanozymes that enables the detection of a few molecules with the naked eye and quantified by an auto-analysis software. The GSH level controls the growth of gold nanoparticles (AuNPs) and generates coloured patterns with distinct tonality, which are then auto-analyzed to calculate the GSH concentrations by smartphone with an auto-analysis software. Under the optimized conditions, grayscale value plotted against GSH concentration exhibited a linear relationship within the range of 25-500 µM with a limit of detection (LoD) of 9.80 µM and highly positive correlation between detected GSH level and TMZ drug-resistance level in GBM cells. This excellent property allowed our approach to be used for on-site determination of GSH levels in a rapid (i.e., within 30 min), simple (i.e., auto-analysis software), and cost-effective process (i.e., instrument-free) for cancer precision therapy.