Cubosomes post-loaded with antimicrobial peptides: characterization, bactericidal effect and proteolytic stability

Abstract

Novel antibiotics, such as antimicrobial peptides (AMPs), have recently attended more and more attraction. In this work, dispersed cubic liquid crystalline gel (cubosomes) was used as drug delivery vehicles for three AMPs (AP114, DPK-060 and LL-37). Association of peptides onto cubosomes was studied at two cubosome/peptide ratios using high performance liquid chromatography, ζ-potential and circular dichroism measurements. AMPs impact on the cubosome structure was investigated using small angle x-ray scattering and cryogenic transmission electron microscopy. The antimicrobial effect of the AMP loaded cubosomes was studied in vitro by minimum inhibitory concentration and time-kill assays. Proteolytic protection was investigated by incubating the formulations with two elastases and the antimicrobial effect after proteolysis was studied using radial diffusion assay. Different association efficacy onto the cubosomes was observed among the AMPs, with LL-37 showing greatest association (>60%). AP114 loaded cubosomes displayed a preserved antimicrobial effect, whereas for LL-37 the broad spectrum bacterial killing was reduced to only comprise Gram-negative bacteria. Interestingly, DPK-060 loaded cubosomes showed a slight enhanced effect against S. aureus and E. coli strains. Moreover, the cubosomes were found to protect LL-37 from proteolytic degradation, resulting in a significantly better bactericidal effect after being subjected to elastase, compared to unformulated peptide.

Bioavailability of nutraceuticals: Role of the food matrix, processing conditions, the gastrointestinal tract, and nanodelivery systems

“…The formation of cubosomes/hexosomes, similar to microemulsions, is followed by titrating the precursor liquid with an aqueous solution until the lipids self‐assemble to form the appropriate colloidal structures. In order to stabilize these colloidal mesophase systems, the block copolymers, such as Pluronic F 127, Poloxamer 707, and Koliphor P 407, are used (Boge et al., 2017; Meikle et al., 2017).…”

Supramolecular structures in lipid digestion and implications for functional food delivery

“…Dispersions of these inverse (oil-continuous) structures in excess water that form cubosomes, hexosomes, and related dispersed systems provide attractive drug and functional food nanocarriers owing to their capability to solubilize not only hydrophobic but also hydrophilic and amphiphilic bioactive molecules [52e58]. The encapsulation of degradation-sensitive molecules such as PUFAs, proteins, and peptides into these structures can protect them from degradation in the biological milieu, which may be crucial for facilitating their transport through the low-pH and protease-rich gastric fluid into the small intestine for absorption [55,59]. The solution conditions such as pH and ionic strength, that are significantly changing during digestion, are important to be taken into account as they affect the intermolecular forces and thereby modify the dynamic self-assembled structural features [47,53,60,61].…”

Reverse micelle-lipid nanocapsules: a novel strategy for drug delivery of the plectasin derivate AP138 antimicrobial peptide

“…Boge et al demonstrated that the high affinity of AMPs to nanoparticles may retard their release, resulting in decreased amounts of free peptide available to exert their antibacterial activity. 34 Indeed, if the drug is presented to bacteria in small quantities over a prolonged period, it may be more effectively neutralized by the microorganisms than if the same quantity is delivered all at once. Thus, the high affinity of the AMPs for nanovectors and prolonged release could result in the loss of antibacterial activity.…”