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Cubosomes for topical delivery of the antimicrobial peptide LL-37
RISE - Research Institutes of Sweden, Bioscience and Materials, Surface, Process and Formulation. Chalmers University of Technology, Sweden.ORCID iD: 0000-0003-4742-1702
RISE - Research Institutes of Sweden, Bioscience and Materials, Surface, Process and Formulation.
RISE - Research Institutes of Sweden, Bioscience and Materials, Surface, Process and Formulation.
RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
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2019 (English)In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 134, p. 60-67Article in journal (Refereed) Published
Abstract [en]

In this study, the use of cubosomes for topical delivery of the antimicrobial peptide (AMP) LL-37 was investigated. Topical delivery of AMPs is of great interest for treatment of skin infections caused by bacteria, such as Staphylococcus aureus. AMP containing cubosomes were produced by three different preparation protocols and compared: (i) pre-loading, where LL-37 was incorporated into a liquid crystalline gel, which thereafter was dispersed into nanoparticles, (ii) post-loading, where LL-37 was let to adsorb onto pre-formed cubosomes, and (iii) hydrotrope-loading, where LL-37 was incorporated during the spontaneously formed cubosomes in an ethanol/glycerol monooleate mixture. Particle size and size distribution were analyzed using dynamic light scattering (DLS), liquid crystalline structure by small angle x-ray scattering (SAXS) and release of LL-37 by a fluorescamine assay. Proteolytic protection of LL-37 as well as bactericidal effect after enzyme exposure was investigated. The skin irritation potential of cubosomes was examined by an in vitro epidermis model. Finally, the bacterial killing property of the cubosomes was examined by an ex vivo pig skin wound infection model with Staphylococcus aureus. Data showed that a high loading of LL-37 induced formation of vesicles in case of cubosomes prepared by sonication (pre-loading). No release of LL-37 was observed from the cubosomes, indicating strong association of the peptide to the particles. Proteolysis studies showed that LL-37 was fully protected against enzymatic attacks while associated with the cubosomes, also denoting strong association of the peptide to the particles. As a consequence, bactericidal effect after enzyme exposure remained, compared to pure LL-37 which was subjected to proteolysis. No skin irritation potential of the cubosomes was found, thus enabling for topical administration. The ex vivo wound infection model showed that LL-37 in pre-loaded cubosomes killed bacteria most efficient.

Place, publisher, year, edition, pages
2019. Vol. 134, p. 60-67
Keywords [en]
alcohol, cathelicidin antimicrobial peptide LL 37, cubosome, drug carrier, fluorescamine, glycerol oleate, hydrotrope, nanoparticle, unclassified drug
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:ri:diva-37674DOI: 10.1016/j.ejpb.2018.11.009PubMedID: 30445164Scopus ID: 2-s2.0-8505687655OAI: oai:DiVA.org:ri-37674DiVA, id: diva2:1283626
Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-01-29Bibliographically approved

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Boge, LukasHåkansson, Joakim

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