The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Veterinary Pharmacology and Toxicology
Volume 11 - 2024 |
doi: 10.3389/fvets.2024.1492543
Colistin-niclosamide-loaded nanoemulsions and nanoemulsion gels for effective therapy of colistin-resistant Salmonella infections
Provisionally accepted
Zhang Junkai
1
Xilong Wang
1*
Pengliang Li
1*
Yanling Gao
2*
Ruiyun Wang
1*
Shuaihua Li
1*
Kaifang Yi
1*
Xiaodie Cui
1*
Gongzheng Hu
1*
Yajun Zhai
1*- 1 Henan Agricultural University, Zhengzhou, China
- 2 Henan Agricultural Vocational College, Zhengzhou, Henan Province, China
Colistin (COL) is regarded as a last-resort treatment for infections by multidrug-resistant (MDR) Gram-negative bacteria. The emergence of colistin-resistant Enterobacterales poses a significant global public health concern. Our study discovered that niclosamide (NIC) reverses COL resistance in Salmonella via a checkerboard assay. However, NIC's poor solubility and bioavailability pose challenges. In this study, we prepared a self-nanoemulsifying drug delivery system (SNEDDS) co-encapsulating NIC and COL. We characterized the physicochemical properties of the resulting colistin-niclosamide-loaded nanoemulsions (COL/NIC-NEs) and colistin-niclosamide-loaded nanoemulsions gels (COL/NIC-NEGs), assessing their antibacterial efficacy in vitro and in vivo. The COL/NIC-NEs exhibited a droplet size of 19.86 nm with a zeta potential of -1.25 mV. COL/NIC-NEs have excellent stability, significantly enhancing the solubility of NIC while also demonstrating a pronounced sustained-release effect. Antimicrobial assays revealed that the MIC of COL in COL/NIC-NEs was reduced by 16-128 times compared to free COL. Killing kinetics and scanning electron microscopy confirmed enhanced antibacterial activity. Antibacterial mechanism studies reveal that the COL/NIC-NEs and COL/NIC-NEGs could enhance the bactericidal activity by damaging cell membranes, disrupting proton motive force (PMF), inhibiting multi-drug efflux pump and promoting oxidative damage. The therapeutic efficacy of the COL/NIC-NEs and COL/NIC-NEGs is further demonstrated in mouse intraperitoneal infection model with COL-resistant Salmonella. To sum up, COL/NIC-NEs and COL/NIC-NEGs was a potential effective strategy promising against COL-resistant Salmonella infections.
Keywords: Colistin, Niclosamide, Bacterial resistance, Salmonella, Nanoemulsions, Nanoemulsion gels
Received: 07 Sep 2024; Accepted: 02 Oct 2024.
Copyright: © 2024 Junkai, Wang, Li, Gao, Wang, Li, Yi, Cui, Hu and Zhai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xilong Wang, Henan Agricultural University, Zhengzhou, China
Pengliang Li, Henan Agricultural University, Zhengzhou, China
Yanling Gao, Henan Agricultural Vocational College, Zhengzhou, 451450, Henan Province, China
Ruiyun Wang, Henan Agricultural University, Zhengzhou, China
Shuaihua Li, Henan Agricultural University, Zhengzhou, China
Kaifang Yi, Henan Agricultural University, Zhengzhou, China
Xiaodie Cui, Henan Agricultural University, Zhengzhou, China
Gongzheng Hu, Henan Agricultural University, Zhengzhou, China
Yajun Zhai, Henan Agricultural University, Zhengzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.