Lipid-Based Liquid Crystals As Carriers for Antimicrobial Peptides: Phase Behavior and Antimicrobial Effect
Artikel i vetenskaplig tidskrift, 2016

The number of antibiotic-resistant bacteria is increasing worldwide, and the demand for novel antimicrobials is constantly growing. Antimicrobial peptides (AMPs) could be an important part of future treatment strategies of various bacterial infection diseases. However, AMPs have relatively low stability, because of proteolytic and chemical degradation. As a consequence, carrier systems protecting the AMPs are greatly needed, to achieve efficient treatments. In addition, the carrier system also must administrate the peptide in a controlled manner to match the therapeutic dose window. In this work, lyotropic liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers for AMPs. These LC structures have the capability of solubilizing both hydrophilic and hydrophobic substances, as well as being biocompatible and biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes and hexosomes) have been studied. Three AMPs have been investigated with respect to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060, and LL-37. Characterization of the LC structures was performed using small-angle X-ray scattering (SAXS), dynamic light scattering, zeta-potential, and cryogenic transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra performance liquid chromatography. The antimicrobial effect of the LCNPs was investigated in vitro using minimum inhibitory concentration (MIC) and time-kill assay. The most hydrophobic peptide (AP114) was shown to induce an increase in negative curvature of the cubic LC system. The most polar peptide (DPK-060) induced a decrease in negative curvature while LL-37 did not change the LC phase at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover, cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial activity, whereas particles loaded with peptide LL-37 displayed a loss in its broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction in antimicrobial activity.

Författare

Lukas Boge

Chalmers University of Technology

SP Sveriges Tekniska Forskningsinstitut

Helena Bysell

SP Sveriges Tekniska Forskningsinstitut

Lovisa Ringstad

SP Sveriges Tekniska Forskningsinstitut

D. Wennman

SP Process Development

Anita Umerska

Micro et Nanomedecines Biomimetiques

V. Cassisa

CHU Angers

J. Eriksson

Uppsala universitet

M. L. Joly-Guillou

CHU Angers

K. Edwards

Uppsala universitet

Martin Andersson

Chalmers, Kemi och kemiteknik, Tillämpad kemi, Teknisk ytkemi

Langmuir

0743-7463 (ISSN) 1520-5827 (eISSN)

Vol. 32 4217-4228

Ämneskategorier

Den kondenserade materiens fysik

DOI

10.1021/acs.langmuir.6b00338