Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand.
Nano Lett
; 18(10): 6207-6213, 2018 10 10.
Article
em En
| MEDLINE
| ID: mdl-30260652
ABSTRACT
Inspired by the fact that chitosan is a representative constituent of the ectocellular structure of Cryptococcus neoformans and a typical biomaterial for improving drug oral absorption, we designed an elegant and efficient C. neoformans-targeted drug delivery system via oral administration. A chitosan-binding peptide screened by phage display was used as the targeting moiety, followed by conjugation to the surface of poly(lactic- co-glycolic acid) nanoparticles as the drug carrier, which was then incubated with free chitosan. The noncovalently bound chitosan adheres to mucus layers and significantly enhances penetration of nanoparticles through the oral absorption barrier into circulation and then re-exposed the targeting ligand for later recognition of the fungal pathogen at the site of infection. After loading itraconazole as a model drug, our drug delivery system remarkably cleared lung infections of C. neoformans and increased survival of model mice. Currently, targeted drug delivery is mainly performed intravenously; however, the system described in our study may provide a universal means to facilitate drug targeting to specific tissues and disease sites by oral administration and may be especially powerful in the fight against increasingly severe fungal infections.
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Base de dados:
MEDLINE
Assunto principal:
Poliésteres
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Sistemas de Liberação de Medicamentos
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Pneumonia Bacteriana
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Nanopartículas
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nano Lett
Ano de publicação:
2018
Tipo de documento:
Article