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Glucosylated nanoparticles for the oral delivery of antibiotics to the proximal small intestine protect mice from gut dysbiosis
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2022-07-07 , DOI: 10.1038/s41551-022-00903-4
Guorong Zhang 1, 2, 3 , Qin Wang 1, 2, 3 , Wanyin Tao 1, 2, 3 , Wei Jiang 1, 2, 3 , Eran Elinav 4, 5 , Yucai Wang 1, 2, 3, 6 , Shu Zhu 1, 2, 3, 6, 7
Affiliation  

Orally delivered antibiotics can reach the caecum and colon, and induce gut dysbiosis. Here we show that the encapsulation of antibiotics in orally administered positively charged polymeric nanoparticles with a glucosylated surface enhances absorption by the proximal small intestine through specific interactions of glucose and the abundantly expressed sodium-dependent glucose transporter 1. This improves bioavailability of the antibiotics, and limits their exposure to flora in the large intestine and their accumulation in caecal and faecal contents. Compared with the standard administration of the same antibiotics, the oral administration of nanoparticle-encapsulated ampicillin, chloramphenicol or vancomycin in mice with bacterial infections in the lungs effectively eliminated the infections, decreased adverse effects on the intestinal microbiota by protecting the animals from dysbiosis-associated metabolic syndromes and from opportunistic pathogen infections, and reduced the accumulation of known antibiotic-resistance genes in commensal bacteria. Glucosylated nanocarriers may be suitable for the oral delivery of other drugs causing gut dysbiosis.



中文翻译:

用于将抗生素口服递送至近端小肠的糖基化纳米颗粒可保护小鼠免受肠道菌群失调

口服抗生素可以到达盲肠和结肠,并引起肠道菌群失调。在这里,我们表明,通过葡萄糖和大量表达的钠依赖性葡萄糖转运蛋白 1 的特异性相互作用,将抗生素封装在具有糖基化表面的口服正电荷聚合物纳米颗粒中,可增强近端小肠的吸收。这提高了抗生素的生物利用度,并且限制它们接触大肠中的菌群以及它们在盲肠和粪便内容物中的积累。与相同抗生素的标准给药相比,纳米颗粒包封的氨苄西林、氯霉素或万古霉素对肺部细菌感染的小鼠口服给药可有效消除感染,通过保护动物免受与生态失调相关的代谢综合征和机会性病原体感染,减少对肠道微生物群的不利影响,并减少共生细菌中已知抗生素抗性基因的积累。糖基化纳米载体可能适用于口服其他引起肠道菌群失调的药物。

更新日期:2022-07-07
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