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Published on: August 11, 2018
Cubosomes for topical delivery of the antimicrobial peptide LL-37
Lukas Boge1, Karin Hallstensson2, Lovisa Ringstad2
1RISE Research Institutes of Sweden, Box 857 SE-50115, Borås, Sweden; Department of Chemistry and Chemical Engineering, Applied Chemistry, Chalmers University of Technology, Göteborg, Sweden.
Abstract:
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.
Insights
Cubosomes effectively deliver antimicrobial peptides (AMPs) like LL-37 for skin infections. Pre-loaded cubosomes demonstrated superior bacterial killing and skin protection in ex vivo models.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Dermatology
Background:
- Topical delivery of antimicrobial peptides (AMPs) is crucial for treating bacterial skin infections.
- Developing effective delivery systems for AMPs like LL-37 is essential for enhancing their stability and efficacy.
- Cubosomes offer a promising nanocarrier system for topical drug delivery due to their unique structure and properties.
Purpose of the Study:
- To investigate the use of cubosomes for the topical delivery of the antimicrobial peptide LL-37.
- To compare three different cubosome preparation protocols for LL-37 loading and efficacy.
- To evaluate the stability, skin irritation potential, and bactericidal activity of LL-37 loaded cubosomes.
Main Methods:
- Cubosomes loaded with LL-37 were prepared using pre-loading, post-loading, and hydrotrope-loading methods.
- Particle characterization involved dynamic light scattering (DLS) and small-angle x-ray scattering (SAXS).
- LL-37 release, proteolytic protection, skin irritation (in vitro), and ex vivo wound infection models were employed.
Main Results:
- Pre-loading resulted in high LL-37 loading and strong association with cubosomes, preventing peptide release.
- LL-37 within cubosomes showed complete protection against enzymatic degradation, retaining bactericidal activity.
- Cubosomes exhibited no skin irritation potential and demonstrated efficient bacterial killing in an ex vivo pig skin wound model.
Conclusions:
- Cubosomes are a stable and non-irritating nanocarrier for topical LL-37 delivery.
- The pre-loading method is most effective for preparing LL-37 cubosomes with enhanced antimicrobial efficacy.
- This study highlights the potential of cubosomes for developing advanced topical treatments for bacterial skin infections.
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