PEG-stabilized lipid disks as carriers for amphiphilic antimicrobial peptides

Abstract

This is an accepted version of a paper published in Journal of Controlled Release. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination.Citation for the published paper: Zetterberg, M., Reijmar, K., Pränting, M., Engström, Å., Andersson, D. et al. (2011) AbstractAntimicrobial 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.

Strategies employed in the design and optimization of synthetic antimicrobial peptide amphiphiles with enhanced therapeutic potentials

“…The PEG-stabilized disks were found to be capable of releasing the bound melittin molecules, which resulted in the disruption of the 5(6)-carboxyfluorescein loaded POPC/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) (90:10 mol%) liposomes [153]. Importantly, the formulation of the cationic AMP in the disks effectively mediated protection against trypsin degradation, which was attributed to steric hindrance to the approach of the protease caused by PEG chains located at the disk rim.…”

Label-Free Characterization of Peptide–Lipid Interactions Using Immobilized Lipodisks

“…As both faces of the lipid bilayer are exposed to the surrounding media, lipodisks are ideal systems for interaction studies. Recent research has also shown that they are potentially useful as drug carriers 24 . Following adequate protocols, lipodisks can be immobilized on a variety of substrates, including quartz crystal microbalance (QCM) 5 and surface plasmon resonance (SPR) 25 sensors , as well as on chromatographic media 5,26,27 .…”

“…These peptides are of great interest in pharmaceutical applications, as some of them have antimicrobial activity. It has been shown that incorporation of these peptides into lipodisks is an excellent way of achieving a sustained release of the compound as well as to protect the peptide from enzymatic degradation 24 . The method described in this report is able to quantify the amount of peptide that can be carried by a lipodisk, as well as the physicochemical parameters describing the peptide-lipodisk association.…”

The efficacy of silver-embedded polypropylene-grafted polyethylene glycol-coated ventricular catheters on prevention of shunt catheter infection in rats

“…In our previous study, we have already shown that PP-g-PEG patches have good soft tissue response, and the biocompatibility of the polymer is increased as more of a PEG side chain is added [14]. Many studies have reported that hydrophilic surfaces, such as PEGgrafted polymers, suppress protein adsorption and platelet adhesion [12,18,45]. These surface characteristics help this graft copolymer to reduce protein deposition that promotes pathogen adhesion and growth on device surfaces [31,35,36].…”