title: Incorporation of antimicrobial peptides in nanostructured lipid membrane mimetic bilayer cubosomes.
abstract: The inverse bicontinuous lipidic cubic phase offers a simple and robust membrane mimetic with the ability to encapsulate peptides, potentially increasing bioavailability, while also offering a platform from which functionalized, targeted nanoparticles can be developed. Herein we have investigated the use of a number of cubic phase nanoparticle systems with encapsulated antimicrobial peptides gramicidin A', melittin, and alamethicin. The optimal peptide loading ranges, over which cubic symmetry was retained, were determined using small angle X-ray scattering. A large variation in peptide loading capability of different cubosome formulations was confirmed using circular dichroism. Observations are supported by particle sizing using dynamic light scattering as well as by direct visualization of nanoparticle morphology using cryogenic transmission electron microscopy. The results are discussed in relation to bilayer properties such as the hydrophobic mismatch between bilayer and peptide, intrinsic surface curvature, and lateral pressure profile of each lipid system. The findings of this study should be of use in the further development of lipid-based peptide encapsulation systems, particularly in the field of drug delivery.
authors.affiliation: Department of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC 3010, Australia; CSIRO Manufacturing, Private Bag 10, Clayton South MDC, VIC 3169, Australia.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Meikle
authors.affiliation: School of Science, College of Science, Engineering and Health, RMIT University, 124 La Trobe Street, Melbourne, VIC 3000, Australia.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Zabara
authors.affiliation: CSIRO Manufacturing, Private Bag 10, Clayton South MDC, VIC 3169, Australia.
authors.forename: Lynne J
authors.initials: LJ
authors.lastname: Waddington
authors.affiliation: Department of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Frances
authors.initials: F
authors.lastname: Separovic
authors.affiliation: School of Science, College of Science, Engineering and Health, RMIT University, 124 La Trobe Street, Melbourne, VIC 3000, Australia. Electronic address: calum.drummond@rmit.edu.au.
authors.forename: Calum J
authors.initials: CJ
authors.lastname: Drummond
authors.affiliation: School of Science, College of Science, Engineering and Health, RMIT University, 124 La Trobe Street, Melbourne, VIC 3000, Australia. Electronic address: charlotte.conn@rmit.edu.au.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Conn
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D000067493:Dynamic Light Scattering; D008051:Lipid Bilayers / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010455:Peptides
keywords: Antimicrobial peptides; Cubic phase; Cubosomes; Nanoparticles; SAXS