Encapsulation into hyaluronic acid-based nanogels improves the selectivity index of the snake cathelicidin Ab-Cath
Nanomedicine Nanotechnology Biology and Medicine, vol. 52, pp. 102694
Abstract
The antimicrobial peptide Ab-Cath, is a promising candidate for development as treatment for antimicrobial resistant (AMR) bacterial infections. Future clinical use is hampered by Ab-Cath's cationic peptidic nature and limited therapeutic window. Here, we evaluated hyaluronic acid-based nanogels for encapsulation of Ab-Cath to circumvent these limitations. Using microfluidics, monodispersed anionic nanogels of 156–232 nm encapsulating >99 % Ab-Cath were prepared. Unprecedented, lyophilization using polyvinyl alcohol and dextran-40 provided Ab-Cath nanogel protection and allowed easy dose adjustment. Lyophilized and redispersed Ab-Cath nanogels were as effective as Ab-Cath solution in killing AMR Staphylococcus aureus, Acinetobacter baumannii and Escherichia coli in biological fluids, and in reducing S. aureus and A. baumannii biofilms. Importantly, encapsulation of Ab-Cath in nanogels reduced Ab-Cath's cytotoxic effects on human fibroblasts by ≥10-fold. Moreover, cutaneous application of Ab-Cath nanogels eliminated bacteria colonizing 3D human skin. These findings affirm the use of nanogels to increase the selectivity index of antimicrobial peptides.
Authors 10
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. Electronic address: M.E.van_Gent@lumc.nl
Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
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Affiliation as printed
Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Electron Microscopy Facility, Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Electron Microscopy Facility, Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
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Affiliation as printed
Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
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