Gelatin emulsion gels loaded with host defence peptides for the treatment of antibiotic-resistant infections

• Published in: Biomaterials advances 2025-01, Vol.166, p.214071, Article 214071
• Main Authors: Mann, Kiran, Aveyard, Jenny, Dallos Ortega, Mateo, Chen, Ting, Koduri, Manohar Prasad, Fothergill, Joanne L., Schache, Andrew G., Curran, Judith M., Poole, Robert J., D'Sa, Raechelle A.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Antimicrobial Peptides - chemistry; Antimicrobial Peptides - pharmacology; Emulsions - chemistry; Emulsions - pharmacology; Encapsulation; Escherichia coli - drug effects; Gelatin; Gelatin - chemistry; Gelatin - pharmacology; Gels; Gels - chemistry; Host defence peptides; Humans; Infection control; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Staphylococcal Infections - drug therapy
• ISSN: 2772-9508; 2772-9508
• DOI: 10.1016/j.bioadv.2024.214071

The surge in multidrug-resistant bacteria against conventional antibiotics is a rapidly developing global health crisis necessitating novel infection management strategies. Host defence peptides (HDPs), also known as antimicrobial peptides (AMPs), offer a promising alternative to traditional antibiotics, but their practical translation is limited by their susceptibility to proteases and potential off-site cytotoxicity. In this paper, we investigate the feasibility of using gelatin emulsion gels (GELs), prepared using a water-in-oil (W/O) method, for the delivery of HDPs DJK-5 and IDR-1018 to improve their clinical utility. DJK-5-loaded GELs exhibited complete eradication of planktonic Methicillin-resistant Staphylococcus aureus (MRSA) at 4 - and 24-h intervals. Similarly, IDR-1018-loaded GELs demonstrated almost complete killing of MRSA and Escherichia coli (E. coli) after 4 h. Importantly, none of the GEL formulations investigated exhibited in vitro cytotoxicity. Overall, these HDP loaded GELs are a promising solution for the treatment of antibiotic-resistant infections. •Gelatin emulsion GELs were used for the delivery of host defence peptides (HDPs).•DJK-5 and IDR-1018 loaded GELs achieved good antimicrobial efficacy against MRSA and E. coli.•DJK-5 and IDR-1018 loaded GELs demonstrated good efficacy for eradication of preformed biofilms of MRSA and E. coli.•Antimicrobial efficacy was demonstrated against lab strain bacteria and clinical isolates.•DJK-5 and IDR-1018 loaded GELs did not display cytotoxicity toward WS1 and L929 cells.