A New Class of Polyion Complex Vesicles (PIC-somes) to Improve Antimicrobial Activity of Tobramycin in Pseudomonas Aeruginosa Biofilms.

Autor: Yildirim T; HIPS - Helmholtz Institute for Pharmaceutical Research Saarland, 66123, Saarbrücken, Germany., Bali A; HIPS - Helmholtz Institute for Pharmaceutical Research Saarland, 66123, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, 66123, Saarbrücken, Germany., Koch M; INM - Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany., Paul P; HIPS - Helmholtz Institute for Pharmaceutical Research Saarland, 66123, Saarbrücken, Germany., Latta L; HIPS - Helmholtz Institute for Pharmaceutical Research Saarland, 66123, Saarbrücken, Germany., Schneider-Daum N; HIPS - Helmholtz Institute for Pharmaceutical Research Saarland, 66123, Saarbrücken, Germany., Gallei M; Polymer Chemistry, Saarland University, Campus C4 2, 66123, Saarbrücken, Germany.; Saarene - Saarland Center for Energy Materials and Sustainability, Campus C4 2, 66123, Saarbrücken, Germany., Lehr CM; HIPS - Helmholtz Institute for Pharmaceutical Research Saarland, 66123, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, 66123, Saarbrücken, Germany.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Oct; Vol. 20 (40), pp. e2401926. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1002/smll.202401926
Abstrakt: Pseudomonas aeruginosa (PA) is a major healthcare concern due to its tolerance to antibiotics when enclosed in biofilms. Tobramycin (Tob), an effective cationic aminoglycoside antibiotic against planktonic PA, loses potency within PA biofilms due to hindered diffusion caused by interactions with anionic biofilm components. Loading Tob into nano-carriers can enhance its biofilm efficacy by shielding its charge. Polyion complex vesicles (PIC-somes) are promising nano-carriers for charged drugs, allowing higher drug loadings than liposomes and polymersomes. In this study, a new class of nano-sized PIC-somes, formed by Tob-diblock copolymer complexation is presented. This approach replaces conventional linear PEG with brush-like poly[ethylene glycol (methyl ether methacrylate)] (PEGMA) in the shell-forming block, distinguishing it from past methods. Tob paired with a block copolymer containing hydrophilic PEGMA induces micelle formation (PIC-micelles), while incorporating hydrophobic pyridyldisulfide ethyl methacrylate (PDSMA) monomer into PEGMA chains reduces shell hydrophilicity, leads to the formation of vesicles (PIC-somes). PDSMA unit incorporation enables unprecedented dynamic disulfide bond-based shell cross-linking, significantly enhancing stability under saline conditions. Neither PIC-somes nor PIC-micelles show any relevant cytotoxicity on A549, Calu-3, and dTHP-1 cells. Tob's antimicrobial efficacy against planktonic PA remains unaffected after encapsulation into PIC-somes and PIC-micelles, but its potency within PA biofilms significantly increases.
(© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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