Antibiotic resistance is a global threat, driven by limited new antimicrobials and rising multidrug-resistant infections. Lipid nanoparticles (LNPs) combine tunable material properties with antimicrobial functionality, providing biocompatibility, controlled release, and biofilm penetration. LNPs provide key advantages over metallic and polymeric nanocarriers, including high biocompatibility, the ability to encapsulate both hydrophilic and hydrophobic agents, controlled release profiles, and reduced cytotoxicity and immune activation. These features enhance drug stability and bioavailability and may help circumvent bacterial defences such as biofilms and efflux pumps. Robust preclinical evaluation platform of antimicrobial biomaterials requires platforms that capture biologically relevant interactions while remaining ethically and economically feasible. The chick embryo model (CEM) has emerged as a versatile platform for infection studies, bridging conventional in vitro assays and mammalian in vivo models. Its vascularized and developing tissue environment enables assessment of nanoparticle biodistribution, local toxicity, and antimicrobial efficacy within a dynamic biological context. This review critically examines the application of the CEM for evaluating LNP-based antimicrobial systems, highlighting current methodological variability and limitations in experimental standardization. By identifying gaps in protocol harmonisation and comparative assessment, this work outlines opportunities to improve reproducibility and translational relevance. Overall, integrating rationally designed LNP systems with optimised CEMs may accelerate the development of next-generation antimicrobial biomaterials to combat antibiotic-resistant infections.
Ruano et al. (Sun,) studied this question.