Hyaluronan-Based Nanohydrogels for Targeting Intracellular S. Aureus in Human Keratinocytes

Montanari, Elita; Oates, Angela; Di Meo, Chiara; Meade, Josephine; Cerrone, Rugiada; Francioso, Antonio; Devine, Deirdre; Coviello, Tommasina; Mancini, Patrizia; Mosca, Luciana; Matricardi, Pietro

Abstract

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Staphylococcus aureus is one of the most significant human pathogens that is frequently isolated in a wide range of superficial and systemic infections. The ability of S. aureus to invade and survive within host cells such as keratinocytes and host immune cells has been increasingly recognized as a potential factor in persistent infections and treatment failures. The incorporation of antibiotics into hyaluronan-cholesterol nanohydrogels represents a novel paradigm in the delivery of therapeutic agents against intracellular bacteria. The work presented herein shows that NHs quickly enter human keratinocytes and accumulate into lysosomes. When used for targeting intracellular S. aureus the antimicrobial activity of loaded levofloxacin is enhanced, possibly changing the antibiotic intracellular fate from cytosol to lysosome. Indeed, gentamicin, an antibiotic that predominantly accumulates in lysosomes, shows significant and equal antibacterial activity when entrapped into NHs. These results strongly suggest that lysosomal formulations may display preferential activity toward intracellular S. aureus, opening new avenues for the use of HA-based NHs for treatment of such skin infections.

Citation

Montanari, E., Oates, A., Di Meo, C., Meade, J., Cerrone, R., Francioso, A., Devine, D., Coviello, T., Mancini, P., Mosca, L., & Matricardi, P. (2018). Hyaluronan-Based Nanohydrogels for Targeting Intracellular S. Aureus in Human Keratinocytes. Advanced Healthcare Materials, 7(12), Article 1701483. https://doi.org/10.1002/adhm.201701483

• Journal Article Type: Article
• Acceptance Date: Mar 16, 2018
• Online Publication Date: Apr 25, 2018
• Publication Date: Jun 20, 2018
• Deposit Date: Jan 16, 2019
• Publicly Available Date: Apr 26, 2019
• Journal: Advanced Healthcare Materials
• Print ISSN: 2192-2640
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 12
• Article Number: 1701483
• DOI: https://doi.org/10.1002/adhm.201701483
• Keywords: Pharmaceutical Science; Biomaterials; Biomedical Engineering
• Public URL: https://hull-repository.worktribe.com/output/1217240
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.201701483
• Related Public URLs: http://eprints.whiterose.ac.uk/129558/
• Contract Date: Jan 17, 2019