Cubosomes for topical delivery of the antimicrobial peptide LL-37
Artikel i vetenskaplig tidskrift, 2019

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.

Cubosome

Topical delivery

Antimicrobial peptide

Skin irritation

LL-37

Proteolysis

Infection

Författare

Lukas Boge

Chalmers, Kemi och kemiteknik, Tillämpad kemi

RISE Research Institutes of Sweden

Karin Hallstensson

RISE Research Institutes of Sweden

Lovisa Ringstad

RISE Research Institutes of Sweden

Jenny Johansson

RISE Research Institutes of Sweden

Therese Andersson

RISE Research Institutes of Sweden

Mina Davoudi

Lunds universitet

Per Tomas Larsson

Innventia

Margit Mahlapuu

Sahlgrenska akademin

Karolinska Institutet

Joakim Håkansson

RISE Research Institutes of Sweden

Martin Andersson

Chalmers, Kemi och kemiteknik, Tillämpad kemi, Martin Andersson Group

European Journal of Pharmaceutics and Biopharmaceutics

0939-6411 (ISSN)

Vol. 134 60-67

Ämneskategorier

Farmaceutisk vetenskap

Fysikalisk kemi

Annan kemi

DOI

10.1016/j.ejpb.2018.11.009

Mer information

Senast uppdaterat

2019-03-04