Peptide-Loaded Cubosomes Functioning as an Antimicrobial Unit against Escherichia coli

Abstract

Dispersions of cubic liquid crystalline phases, also known as cubosomes, have shown great promise as delivery vehicles for a wide range of medicines. Due to their ordered structure, comprising alternating hydrophilic and hydrophobic domains, cubosomes possess unique delivery properties and compatibility with both water-soluble and -insoluble drugs. However, the drug delivery mechanism and cubosome interaction with human cells and bacteria are still poorly understood. Herein, we reveal how cubosomes loaded with the human cathelicidin antimicrobial peptide LL-37, a system with high bacteria-killing effect, interact with the bacterial membrane and provide new insights into the eradication mechanism. Combining the advanced experimental techniques neutron reflectivity and quartz crystal microbalance with dissipation monitoring, a mechanistic drug delivery model for LL-37-loaded cubosomes on bacterial mimicking bilayers was constructed. Moreover, the cubosome interaction with Escherichia coli was directly visualized using super-resolution laser scanning microscopy and cryogenic electron tomography. We could conclude that cubosomes loaded with LL-37 adsorbed and distorted bacterial membranes, providing evidence that the peptide-loaded cubosomes function as an antimicrobial unit.

Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields

“…The authors suggested that the bactericidal effect was due to physical interaction between the product and the bacterial membrane and not solely to the release of the peptide. Moreover, they noted that the presence of LL-37, the chosen AMP, constituted of a secondary structure of a linear α-helix increased the affinity of CB to bacterial membranes ( Boge et al, 2017 ; Boge et al, 2019a ; Boge et al, 2019b ).…”

Microfluidic technologies for the synthesis and manipulation of biomimetic membranous nano-assemblies

“…[61][62][63] Cubosomes have been shown to provide a certain degree of in vivo protection to biomolecules that would otherwise be sensitive to enzymatic degradation, highly advantageous in the delivery of immunogenic therapeutics. [62][63][64] Timely and impressive work from Sarkar et al used cubosomal particles for the delivery of genetic material, attributing improved delivery efficiency to particle topology. 65 There is potential for enhancing site specificity by leveraging the polymeric corona, and some preliminary work has gone into producing stimuli-responsive cubosomal particles for environmentally triggered cargo release.…”

Phytantriol-Based Cubosome Formulation as an Antimicrobial against Lipopolysaccharide-Deficient Gram-Negative Bacteria

“…Although various mimetic bacterial membranes have been reconstituted on the surface for antibiotics-membranes studies, to reduce the total charge of lipid mixtures, most of the lipids compositions were mixed with zwitterionic phosphatidylcholines (PC), which were not found in bacterial membranes. Those membranes include zwitterionic single-lipid 1-palmitoyl-2oleoyl-sn-glycero-3-phosphocholine (POPC) 56 and (dioleylphosphatidylcholine) DOPC 57,58 bilayer, or anionic POPG:-POPC 59 and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC): 1,2-dimyristoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DMPG) 60 with less than 25% of the negative charges to represent the bacterial membrane. In 2015 Lind and coworkers extracted lipids from E. coli with low net negative charges (75% PE, 13% PG, and 12% CL) 61 and had successfully reconstituted the bacterial membrane by the vesicle rupture for NR study.…”