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Release of beta-galactosidase from poloxamine/alfa-cyclodextrin hydrogels

机译:从poloxamine / alfa-cyclodextrin hydrogels释放β-半乳糖苷酶

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摘要

All mammals lose their ability to produce lactase (β-galactosidase), the enzyme that cleaves lactose into galactose and glucose, afterweaning. The prevalence of lactase deficiency (LD) spans from 2 to 15% among northern Europeans, to nearly 100% amongAsians. Following lactose consumption, people with LD often experience gastrointestinal symptoms such as abdominal pain, boweldistension, cramps and flatulence, or even systemic problems such as headache, loss of concentration and muscle pain. These symptomsvary depending on the amount of lactose ingested, type of food and degree of intolerance. Although those affected can avoidthe uptake of dairy products, in doing so, they lose a readily available source of calcium and protein. In this work, gels obtained bycomplexation of Tetronic 90R4 with α-cyclodextrin loaded with β-galactosidase are proposed as a way to administer the enzymeimmediately before or with the lactose-containing meal. Both molecules are biocompatible, can form gels in situ, and showsustained erosion kinetics in aqueous media. The complex was characterized by FTIR that evidenced an inclusion complex betweenthe polyethylene oxide block and α-cyclodextrin. The release profiles of β-galactosidase from two different matrices (gels andtablets) of the in situ hydrogels have been obtained. The influence of the percentage of Tetronic in media of different pH was evaluated.No differences were observed regarding the release rate from the gel matrices at pH 6 (t50 = 105 min). However, in the case ofthe tablets, the kinetics were faster and they released a greater amount of 90R4 (25%, t50 = 40–50 min). Also, the amount ofenzyme released was higher for mixtures with 25% Tetronic. Using suitable mathematical models, the corresponding kinetic parametershave been calculated. In all cases, the release data fit quite well to the Peppas–Sahlin model equation, indicating that therelease of β-galactosidase is governed by a combination of diffusion and erosion processes. It has been observed that the diffusionmechanism prevails over erosion during the first 50 minutes, followed by continued release of the enzyme due to the disintegrationof the matrix.
机译:断奶后,所有哺乳动物都会丧失产生乳糖酶(β-半乳糖苷酶)的能力,该酶将乳糖分解为半乳糖和葡萄糖。北欧人中乳糖酶缺乏症(LD)的患病率从2%到15%不等,而在亚洲人中则接近100%。摄入乳糖后,LD患者经常会出现胃肠道症状,例如腹痛,肠胀,痉挛和肠胃气胀,甚至出现全身性问题,例如头痛,注意力不集中和肌肉疼痛。这些症状取决于摄入的乳糖量,食物类型和不耐受程度。尽管受影响的人可以避免摄取乳制品,但这样做会损失钙和蛋白质的现成来源。在这项工作中,提出了通过将Tetronic 90R4与负载有β-半乳糖苷酶的α-环糊精复合获得的凝胶,作为在含乳糖餐前或与含乳糖餐一起立即施用酶的方法。两种分子都是生物相容性的,可以原位形成凝胶,并在水性介质中显示出持续的腐蚀动力学。该复合物的特征在于FTIR,其证明了聚环氧乙烷嵌段和α-环糊精之间的包合物。从原位水凝胶的两种不同基质(凝胶和片剂)获得了β-半乳糖苷酶的释放曲线。评估了Tetronic在不同pH的介质中所占百分比的影响。在pH 6(t50 = 105分钟)下,凝胶基质的释放速率没有观察到差异。但是,对于片剂,动力学更快,释放出更多的90R4(25%,t50 = 40-50分钟)。同样,对于含25%Tetronic的混合物,释放的酶量更高。使用合适的数学模型,已经计算出了相应的动力学参数。在所有情况下,释放数据都非常适合Peppas-Sahlin模型方程,表明β-半乳糖苷酶的释放受扩散和侵蚀过程的共同控制。已经观察到,在最初的50分钟内,扩散机制胜过腐蚀,随后由于基质的分解,酶继续释放。

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