Beyond the Charge: Interplay of Nanogels' Functional Group and Zeta-Potential for Antifungal Drug Delivery to Human Pathogenic Fungus Aspergillus Fumigatus.

Autor: Vogel T; Department for Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication, University of Würzburg, 97070, Würzburg, Germany., Kohlmann S; Department for Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication, University of Würzburg, 97070, Würzburg, Germany., Abboud Z; Department of Internal Medicine II, Center for Experimental Molecular Medicine, Würzburg University Hospital, 97078, Würzburg, Germany., Thusek S; Department of Internal Medicine II, Center for Experimental Molecular Medicine, Würzburg University Hospital, 97078, Würzburg, Germany., Fella F; Department for Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication, University of Würzburg, 97070, Würzburg, Germany., Teßmar J; Department for Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication, University of Würzburg, 97070, Würzburg, Germany., Sekimizu K; Endowed Course 'Drug Discoveries by Silkworm Models,', Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, 192-0395, Japan., Miyashita A; Institute of Medical Mycology, Teikyo University, Tokyo, 192-0395, Japan., Beilhack A; Department of Internal Medicine II, Center for Experimental Molecular Medicine, Würzburg University Hospital, 97078, Würzburg, Germany., Groll J; Department for Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication, University of Würzburg, 97070, Würzburg, Germany., Yu Y; Department of Internal Medicine II, Center for Experimental Molecular Medicine, Würzburg University Hospital, 97078, Würzburg, Germany.; JSPS International Research Fellow Endowed Course 'Drug Discoveries by Silkworm Models,', Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, 192-0395, Japan., Albrecht K; Department for Functional Materials in Medicine and Dentistry, Institute of Functional Materials and Biofabrication, University of Würzburg, 97070, Würzburg, Germany.
Jazyk: angličtina
Zdroj: Macromolecular bioscience [Macromol Biosci] 2024 Sep; Vol. 24 (9), pp. e2400082. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1002/mabi.202400082
Abstrakt: The ubiquitous mold Aspergillus fumigatus (A. fumigatus) is one of the main fungal pathogens causing invasive infections in immunocompromised humans. Conventional antifungal agents exhibit limited efficacy and often cause severe side effects. Nanoparticle-based antifungal delivery provides a promising alternative, which can increase local drug concentration; while, mitigating toxicity, thereby enhancing treatment efficacy. Previous research underscores the potential of poly(glycidol)-based nanogels (NG) with negative surface charge as carriers for delivering antifungals to A. fumigatus hyphae. In this study, NG is tailored with 2-carboxyethyl acrylate (CEA) or with phosphoric acid 2-hydroxyethyl acrylate (PHA). It is discovered that quenching with PHA clearly improves the adhesion of NG to hyphal surface and the internalization of NG into the hyphae under protein-rich conditions, surpassing the outcomes of non-quenched and CEA-quenched NG. This enhancement cannot be solely attributed to an increase in negative surface charge but appears to be contingent on the functional group of the quencher. Further, it is demonstrated that itraconazole-loaded, PHA-functionalized nanogels (NGxPHA-ITZ) show lower MIC in vitro and superior therapeutic effect in vivo against A. fumigatus compared to pure itraconazole. This confirms NGxPHA as a promising antifungal delivery system.
(© 2024 The Author(s). Macromolecular Bioscience published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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