PEG-stabilized lipid disks as carriers for amphiphilic antimicrobial peptides

• Published in: Journal of controlled release 2011-12, Vol.156 (3), p.323-328
• Main Authors: Zetterberg, Malin M., Reijmar, Karin, Pränting, Maria, Engström, Åke, Andersson, Dan I., Edwards, Katarina
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; antibacterial properties; Antimicrobial peptide; antimicrobial peptides; bacteria; Biological and medical sciences; Drug Carriers - chemistry; E. coli; electron microscopy; Escherichia coli; Escherichia coli - drug effects; Escherichia coli Infections - drug therapy; General pharmacology; Humans; Lipids - chemistry; Medical sciences; Melitten - administration & dosage; Melitten - chemistry; Melitten - metabolism; Melitten - pharmacology; Melittin; Molecular Sequence Data; PEG-stabilized lipid disk; peptide antibiotics; Peptide delivery; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Proteolysis
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2011.08.029

Antimicrobial peptides hold potential as a possible alternative, or complement, to conventional antibiotics but new, safe and efficient means are needed for formulation and administration of the peptides. In this study we have investigated the utility of a novel type of lipid particles, the polyethylene glycol-stabilized lipid disks, as carriers for the model peptide melittin. The structural integrity of the carrier particle when loaded with the peptide was investigated using cryo-transmission electron microscopy. Liposome leakage upon addition of the peptide–lipid disks was monitored as a means to verify the membrane lytic effect of the formulation. The susceptibility of melittin to tryptic digestion was studied and compared in the absence and presence of lipid disks. Finally, the antibacterial effect of the peptide–lipid disk formulation was compared to that of free melittin after both single and repeated exposure to Escherichia coli. The results show that melittin can redistribute from the disk into a new host membrane and that formulation in the disks does not compromise melittin's membrane permeabilizing ability. Further, the peptide was found to be fully protected against degradation when bound to the disks. Time-kill experiments revealed that all the antibacterial effect of melittin administered in free form was gone after a single exposure to E. coli. In contrast, the disk formulation showed significant cell-killing effect also upon a second exposure to bacteria, indicating an extended release of peptide from the lipid disks. These results suggest that the lipid disks constitute a new class of promising carriers for peptide antibiotics. [Display omitted]