Journal
NATURE BIOMEDICAL ENGINEERING
Volume 6, Issue 7, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41551-022-00903-4
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Funding
- National Key R&D Program of China [2017YFA0205600, 2018YFA0508000]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB29030101]
- National Natural Science Foundation of China [52025036, 82061148013, 81821001, 51903105]
- Shanghai Municipal Science and Technology Major Project
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Encapsulating antibiotics in orally administered positively charged polymeric nanoparticles with a glucosylated surface improves absorption in the proximal small intestine and limits exposure to flora in the large intestine.
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. The encapsulation of antibiotics in glucosylated polymeric nanoparticles that are readily absorbed by the proximal small intestine improves the bioavailability of the antibiotics and limits their exposure to flora in the large intestine.
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