Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 193, Issue -, Pages 254-261Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2023.11.005
Keywords
Antimicrobial peptides; SAAP-148; Ab-Cath; Antimicrobial resistance; Bacterial infections; Nanogel; Drug delivery
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This study evaluated the encapsulation of two antimicrobial peptides (AMPs) into nanogels to improve their selectivity index. The nanogels showed similar activity to AMP solutions against antimicrobial resistant bacteria and reduced cytotoxicity towards human cells, thereby increasing their potential as therapeutics.
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.
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