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

Year of Publication:

2023

Publication:

2023

Contained In:

To Main Record - volume:193

Contained In:

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V - 193(2023) vom: 09. Dez., Seite 254-261

Language:

English

Contributors:

van Gent, Miriam E [Author]
Klodzinska, Sylvia N [Author]
Drijfhout, Jan Wouter [Author]
Nielsen, Hanne M [Author]
Nibbering, Peter H [Author]

Links:

Volltext

Keywords:

Ab-Cath
Antimicrobial peptides
Antimicrobial resistance
Bacterial infections
Drug delivery
Journal Article
Nanogel
SAAP-148

Notes:

Date Revised 06.12.2023

published: Print-Electronic

Citation Status In-Process

doi:

10.1016/j.ejpb.2023.11.005

funding:

Supporting institution / Project title:

PPN (Catalogue-ID):

NLM364502134