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载阿莫西林壳聚糖纳米粒与菊粉联用:一种减轻幽门螺杆菌治疗中抗生素耐药性和维持肠道菌群平衡的新策略。

Co-administration of amoxicillin-loaded chitosan nanoparticles and inulin: A novel strategy for mitigating antibiotic resistance and preserving microbiota balance in Helicobacter pylori treatment.

机构信息

Research Institute of Medical & Health Sciences, University of Sharjah, 27272 Sharjah, United Arab Emirates; Chemistry of Natural and Microbial Product Department, National Research Centre, Cairo 12622, Egypt.

Research Institute of Medical & Health Sciences, University of Sharjah, 27272 Sharjah, United Arab Emirates.

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 2):126706. doi: 10.1016/j.ijbiomac.2023.126706. Epub 2023 Sep 7.

Abstract

Helicobacter pylori (H. pylori) is a causative agent of various gastrointestinal diseases and eradication mainly relies on antibiotic treatment, with (AMX) being a key component. However, rising antibiotic resistance in H. pylori necessitates the use of antibiotics combination therapy, often disrupting gut microbiota equilibrium leading to further health complications. This study investigates a novel strategy utilizing AMX-loaded chitosan nanoparticles (AMX-CS NPs), co-administered with prebiotic inulin to counteract H. pylori infection while preserving microbiota health. Following microbroth dilution method, AMX displayed efficacy against H. pylori, with a MIC of 48.34 ± 3.3 ng/mL, albeit with a detrimental impact on Lactobacillus casei (L. casei). The co-administration of inulin (500 μg/mL) with AMX restored L. casei viability while retaining the lethal effect on H. pylori. Encapsulation of AMX in CS-NPs via ionic gelation method, resulted in particles of 157.8 ± 3.85 nm in size and an entrapment efficiency (EE) of 86.44 ± 2.19 %. Moreover, AMX-CS NPs showed a sustained drug release pattern over 72 h with no detectable toxicity on human dermal fibroblasts cell lines. Encapsulation of AMX into CS NPs also reduced its MIC against H. pylori, while its co-administration with inulin maintained L. casei viability. Interestingly, treatment with AMX-CS NPs also reduced the expression of the efflux pump gene hefA in H. pylori. This dual treatment strategy offers a promising approach for more selective antimicrobial treatment, minimizing disruption to healthy microbial communities while effectively addressing pathogenic threats.

摘要

幽门螺杆菌(H. pylori)是多种胃肠道疾病的致病因子,其根除主要依赖于抗生素治疗,其中(AMX)是关键成分。然而,H. pylori 抗生素耐药性的上升要求使用抗生素联合治疗,这往往会破坏肠道微生物群落平衡,导致进一步的健康并发症。本研究探讨了一种利用载 AMX 壳聚糖纳米粒(AMX-CS NPs)与益生元菊糖联合应用的新策略,以抵抗 H. pylori 感染,同时保持微生物群落健康。采用微量肉汤稀释法,AMX 对 H. pylori 显示出疗效,其 MIC 为 48.34±3.3ng/mL,但对乳酸乳球菌(L. casei)有不利影响。与 AMX 联合使用菊糖(500μg/mL)可恢复 L. casei 的活力,同时保持对 H. pylori 的致死作用。通过离子凝胶化法将 AMX 包封在 CS-NPs 中,得到粒径为 157.8±3.85nm 的颗粒,包封效率(EE)为 86.44±2.19%。此外,AMX-CS NPs 在 72 小时内呈现出持续的药物释放模式,对人皮肤成纤维细胞系无检测到毒性。将 AMX 包封在 CS NPs 中还降低了其对 H. pylori 的 MIC,同时与菊糖联合使用可维持 L. casei 的活力。有趣的是,用 AMX-CS NPs 治疗还降低了 H. pylori 外排泵基因 hefA 的表达。这种双重治疗策略为更具选择性的抗菌治疗提供了一种有前途的方法,最大限度地减少了对健康微生物群落的干扰,同时有效地解决了致病威胁。

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