Encapsulation in oleyl-modified hyaluronic acid nanogels substantially improves the clinical potential of the antimicrobial peptides SAAP-148 and Ab-Cath
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
Antimicrobial peptides (AMPs) are promising alternatives to antibiotics for treatment of antimicrobial resistant (AMR) bacterial infections. However, their narrow therapeutic window due to in vivo toxicity and limited stability hampers their clinical use. Here, we evaluated encapsulation of two amphiphilic AMPs, SAAP-148 and snake cathelicidin Ab-Cath, into oleyl-modified hyaluronic acid (OL-HA) nanogels to improve their selectivity index. The AMP-loaded OL-HA nanogels ranged 181-206 nm in size with a PDI of 0.2, highly negative surface charge (-47 to -48 mV) and moderate encapsulation efficiency (53-63%). The AMP-loaded OL-HA nanogels displayed similar activity in vitro as AMP solutions against AMR Staphylococcus aureus and Acinetobacter baumannii, with a dose-dependent effect over time. Importantly, the AMP-loaded OL-HA nanogels showed decreased cytotoxicity towards human erythrocytes and primary skin fibroblast, thereby improving the selectivity index of SAAP-148 and Ab-Cath by 2- and 16.8-fold, respectively. Particularly, the selectivity of Ab-Cath-loaded OL-HA nanogels has great clinical potential, with an index that reached ≥ 300 for S. aureus and ≥ 3000 for A. baumannii. These findings indicate that OL-HA nanogels are a promising drug delivery system to reduce the cytotoxicity of AMPs without substantially affecting their antimicrobial activity, thereby increasing their selectivity index and potential as therapeutics to combat AMR bacterial infections.
| Media Type: |
Electronic Article |
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| Year of Publication: |
2023 |
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| Publication: |
2023 |
| Contained In: |
To Main Record - volume:193 |
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| Contained In: |
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V - 193(2023) vom: 01. Dez., Seite 254-261 |
| Language: |
English |
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| Contributors: |
van Gent, Miriam E [Author] |
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| Links: |
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| Notes: |
Date Completed 11.12.2023 Date Revised 11.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejpb.2023.11.005 |
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| funding: |
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| Supporting institution / Project title: |
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| 520 | |a Antimicrobial peptides (AMPs) are promising alternatives to antibiotics for treatment of antimicrobial resistant (AMR) bacterial infections. However, their narrow therapeutic window due to in vivo toxicity and limited stability hampers their clinical use. Here, we evaluated encapsulation of two amphiphilic AMPs, SAAP-148 and snake cathelicidin Ab-Cath, into oleyl-modified hyaluronic acid (OL-HA) nanogels to improve their selectivity index. The AMP-loaded OL-HA nanogels ranged 181-206 nm in size with a PDI of 0.2, highly negative surface charge (-47 to -48 mV) and moderate encapsulation efficiency (53-63%). The AMP-loaded OL-HA nanogels displayed similar activity in vitro as AMP solutions against AMR Staphylococcus aureus and Acinetobacter baumannii, with a dose-dependent effect over time. Importantly, the AMP-loaded OL-HA nanogels showed decreased cytotoxicity towards human erythrocytes and primary skin fibroblast, thereby improving the selectivity index of SAAP-148 and Ab-Cath by 2- and 16.8-fold, respectively. Particularly, the selectivity of Ab-Cath-loaded OL-HA nanogels has great clinical potential, with an index that reached ≥ 300 for S. aureus and ≥ 3000 for A. baumannii. These findings indicate that OL-HA nanogels are a promising drug delivery system to reduce the cytotoxicity of AMPs without substantially affecting their antimicrobial activity, thereby increasing their selectivity index and potential as therapeutics to combat AMR bacterial infections | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Ab-Cath | |
| 650 | 4 | |a Antimicrobial peptides | |
| 650 | 4 | |a Antimicrobial resistance | |
| 650 | 4 | |a Bacterial infections | |
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| 700 | 1 | |a Nielsen, Hanne M |e verfasserin |4 aut | |
| 700 | 1 | |a Nibbering, Peter H |e verfasserin |4 aut | |
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