Mechanoresponsive materials can harness mech. forces to initiate mol. events and alter their physicochem. properties.Enzyme reactions, which enable diverse chem. transformations under mild conditions, have great potential as outputs of the mechanoresponse, especially in biol. applications.Here, we present a hydrogel-based platform that realizes mechanotransduction to enzyme reactions through the modulation of multivalent salt-bridge interactions between a polymeric inhibitor incorporated within the gel network and an enzyme in the gel matrix.As a proof-of-concept study, two types of hydrogels were developed: ^BGGu-gel with β-galactosidase and ^TBGu-gel with thrombin.The BGGu-gel, containing a chromogenic substrate, exhibits mechanochromism, visually mapping the mech. load onto the gel via a colorimetric response.The ^TBGu-gel, containing fibrinogen as a substrate, displays self-growth, achieving enhanced mech. strength under stress through thrombin-mediated hydrolysis of fibrinogen into fibrin, followed by the spontaneous formation of fibrin fibers as an addnl. gel network.

2024-01-01·International Journal of Biological Macromolecules

Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance

Article

作者: Iglesias, Susana ; Fraile-Gutiérrez, Isabel ; Acosta, Niuris ; Revuelta, Julia

β-Galactosidase supplementation plays an important role in the life of people with lactose intolerance. However, these formulations are rendered ineffective by the low pH and pepsin in the stomach and pancreatic proteases in the intestine. Therefore, it is necessary to develop oral transport systems for carrying this enzyme in the active form up to the intestine, where the lactose digestion occurs. In this research, a new hydrogel was developed that could potentially be used for enzyme supplement therapy. In this regard, the chitosan-based β-Gal formulations described in the manuscript are an alternative long-acting preparation to the so far available preparations that allow for enzyme protection and mucosal targeting. These hydrogels were prepared from chitosan and polyethylene glycol and contained a covalently immobilized β-galactosidase from Aspergillus oryzae. The β-galactosidase in the hydrogel was protected from degradation in a gastric medium at a pH of 2.5 and retained 75 % of its original activity under subsequent intestinal conditions. In the case of a simulated gastric fluid with a pH of 1.5, a copolymer containing methacrylic acid functional groups was sufficient to protect the hybrid hydrogel from the extremely acidic pH. In addition, the surface of the hydrogel was chemically modified with thiol and amidine groups, which increased the binding to intestinal mucin by 20 % compared with the unmodified hydrogel. These results represent a promising approach for oral transport as a reservoir for β-galactosidase in the small intestine to reduce the symptoms of hypolactasia.

2022-03-01·Journal of Inherited Metabolic Disease2区 · 医学

β‐Galactosidase therapy can mitigate blood galactose elevation after an oral lactose load in galactose mutarotase deficiency

2区 · 医学

Article

作者: Arai‐Ichinoi, Natsuko ; Kure, Shigeo ; Wada, Yoichi ; Kikuchi, Atsuo

AbstractGalactose mutarotase (GALM) deficiency (MIM# 618881), also known as type IV galactosemia, is caused by biallelic pathogenic variants of GALM. Cataracts are observed in patients with GALM deficiency as well as in other conditions associated with high levels of blood galactose and can be prevented by consuming a galactose‐restricted diet or formula. Galactose restriction is the only known treatment for GALM deficiency and other types of galactosemia. We incidentally found that β‐galactosidase might reduce blood galactose levels caused by lactose loading in GALM deficiency. Consequently, we investigated the effectiveness of β‐galactosidase in decreasing the level of blood galactose in three patients with GALM deficiency. We performed two lactose loading tests per case: one with and one without β‐galactosidase. The add‐on administration of β‐galactosidase significantly mitigated blood galactose elevations after lactose loading. Although urine galactitol was mildly elevated in all patients with GALM deficiency, β‐galactosidase did not prevent increased levels of urine galactitol during the loading tests. No adverse events, including cataracts, were observed during or after the tests. Therefore, β‐galactosidase could be a potential novel treatment agent for blood galactose elevation caused by lactose in patients with GALM deficiency. The effectiveness of β‐galactosidase could possibly result in loosening of the galactose dietary restrictions or treatment for patients with GALM deficiency.

100 项与半乳糖苷酶(Takata Seiyaku) 相关的药物交易

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