Haitao Yu, Sampa Sarkar, Z. L. Shaw, Brendan Dyett, Xudong Cai, Sue Lyn Yap, Charlotte E. Conn, Aaron Elbourne, Calum J. Drummond, Jiali Zhai
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Ionizable Lipid Containing Nanocarriers for Antimicrobial Agent Delivery
Antimicrobial resistance (AMR) poses a global health crisis demanding innovative solutions. Traditional antibiotics, though pivotal over the past century in combating bacterial infections, face diminished efficacy against evolving bacterial defense mechanisms, especially in Gram-negative strains. This study explores self-assembled ionizable lipid nanoparticles (LNPs) with the incorporation of two ionizable lipid components (one cationic, one anionic) in nanocarriers for advanced antimicrobial drug delivery of the broad-spectrum antibiotic Piperacillin (Pip). Incorporating cationic ionizable lipid ALC-0315, recognized as a functional lipid in the Pfizer-BioNTech mRNA-based SARS-CoV-2 vaccine, into LNPs allowed mesophase transition, pH responsiveness, and ionization behavior in acidic environments found in sites of bacterial infections, to be studied using synchrotron small angle X-ray scattering, dynamic light scattering, and a 2-(p-toluidino)-6-naphthalene sulfonic acid assay. Incorporating another anionic ionizable lipid, oleic acid not only modulates the LNPs’ physicochemical properties, such as size, internal phase nanostructure, and surface charge but also synergistically enhances the antimicrobial potency together with ALC-0315 with a benefit enhancing permeability and fusion with bacterial membranes. This study introduces a strategy for tailoring ionizable lipid compositions in LNPs, providing a new approach to antimicrobial treatment contributing to the fight against AMR.
期刊介绍:
Small Science is a premium multidisciplinary open access journal dedicated to publishing impactful research from all areas of nanoscience and nanotechnology. It features interdisciplinary original research and focused review articles on relevant topics. The journal covers design, characterization, mechanism, technology, and application of micro-/nanoscale structures and systems in various fields including physics, chemistry, materials science, engineering, environmental science, life science, biology, and medicine. It welcomes innovative interdisciplinary research and its readership includes professionals from academia and industry in fields such as chemistry, physics, materials science, biology, engineering, and environmental and analytical science. Small Science is indexed and abstracted in CAS, DOAJ, Clarivate Analytics, ProQuest Central, Publicly Available Content Database, Science Database, SCOPUS, and Web of Science.