Liquid crystal nanoparticles for oral combination antibiotic therapies: A strategy towards protecting commensal gut bacteria during treatment.

Autor: He X; Department of Pharmacy, Uppsala University, Uppsala, Sweden; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Uppsala, Sweden; Uppsala Antibiotic Center, Uppsala University, Uppsala, Sweden., Karlsson PA; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden., Xiong R; Department of Chemistry, Uppsala University, Uppsala, Sweden., Moodie LWK; Uppsala Antibiotic Center, Uppsala University, Uppsala, Sweden; Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden., Wang H; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden., Bergström CAS; Department of Pharmacy, Uppsala University, Uppsala, Sweden; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Uppsala, Sweden; Uppsala Antibiotic Center, Uppsala University, Uppsala, Sweden., Hubert M; Department of Pharmacy, Uppsala University, Uppsala, Sweden; Uppsala Antibiotic Center, Uppsala University, Uppsala, Sweden. Electronic address: madlen.hubert@farmaci.uu.se.
Jazyk: angličtina
Zdroj: Journal of colloid and interface science [J Colloid Interface Sci] 2025 Jan 15; Vol. 678 (Pt B), pp. 287-300. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1016/j.jcis.2024.08.230
Abstrakt: Antibiotics are essential for treating infections and reducing risks during medical interventions. However, many commonly used antibiotics lack the physiochemical properties for an efficient oral administration when treating systemic infection. Instead, we are reliant on intravenous delivery, which presents complications outside of clinical settings. Developing novel formulations for oral administration is a potential solution to this problem. We engineered hexosome and cubosome liquid crystal nanoparticles (LCNPs) characterized by small-angle X-ray scattering and cryogenic transmission electron microscopy, and could encapsulate the antibiotics vancomycin (VAN) and clarithromycin (CLA) with high loading efficiencies. By rationally choosing stable lipid building blocks, the loaded LCNPs demonstrated excellent resilience against enzymatic degradation in an in vitro gut model LCNP stability is crucial as premature antibiotic leakage can negatively impact the gut microbiota. In screens against the representative gut bacteria Enterococcus faecalis and Escherichia coli, our LCNPs provided a protective effect. Furthermore, we explored co-administration and dual loading strategies of VAN and CLA, and demonstrated effective loading, stability and protection for E. faecalis and E. coli. This work represents a proof of concept for the early-stage development of antibiotic-loaded LCNPs to treat systemic infection via oral administration, opening opportunities for combination antibiotic therapies.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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