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.
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