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

Lukas Boge, Anita Umerska, Nada Matougui, Helena Bysell, Lovisa Ringstad, Mina Davoudi, Jonny Eriksson, Katarina Edwards, Martin Andersson

Research output: Contribution to journalArticlepeer-review

68 Citations (SciVal)


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.

Original languageEnglish
Pages (from-to)400-412
Number of pages13
JournalInternational Journal of Pharmaceutics
Issue number1-2
Publication statusPublished - 2017 Jun 30

Subject classification (UKÄ)

  • Pharmacology and Toxicology


  • Amp
  • Antimicrobial peptide
  • Cubosome
  • Glycerol monooleate
  • Liquid crystalline nanoparticle
  • Proteolysis


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