Glucosylated nanoparticles for the oral delivery of antibiotics to the proximal small intestine protect mice from gut dysbiosis

Nat Biomed Eng. 2022 Jul;6(7):867-881. 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 ⁶ ⁷ ⁸ ⁹, Shu Zhu ¹⁰ ¹¹ ¹² ¹³ ¹⁴

Affiliations

1 Department of Digestive Disease and Intelligent Nanomedicine Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
2 Institute of Immunology, University of Science and Technology of China, Hefei, China.
3 The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
4 Systems Immunology Department, Weizmann Institute of Science, Rehovot, Israel.
5 Microbiome & Cancer Division, DKFZ, Heidelberg, Germany.
6 Department of Digestive Disease and Intelligent Nanomedicine Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. [email protected].
7 Institute of Immunology, University of Science and Technology of China, Hefei, China. [email protected].
8 The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. [email protected].
9 Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China. [email protected].
10 Department of Digestive Disease and Intelligent Nanomedicine Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. [email protected].
11 Institute of Immunology, University of Science and Technology of China, Hefei, China. [email protected].
12 The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. [email protected].
13 Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China. [email protected].
14 School of Data Science, University of Science and Technology of China, Hefei, China. [email protected].
# Contributed equally.

PMID: 35798834 DOI: 10.1038/s41551-022-00903-4

Abstract

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.

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