Subcellular localization and therapeutic efficacy of polymeric micellar nanoparticles encapsulating bedaquiline for tuberculosis treatment in zebrafish

Bhandari, M. ; Soria-Carrera, H. ; Wohlmann, J. ; Knudsen Dal, N. J. ; Martínez de la Fuente, J. ; Martín-Rapún, R. (Universidad de Zaragoza) ; Griffiths, G. ; Fenaroli, F.

Resumen: The combination drug regimens that have long been used to treat tuberculosis (TB), caused by Mycobacterium tuberculosis, are fraught with problems such as frequent administration, long duration of treatment, and harsh adverse effects, leading to the emergence of multidrug resistance. Moreover, there is no effective preventive vaccine against TB infection. In this context, nanoparticles (NPs) have emerged as a potential alternative method for drug delivery. Encapsulating antibiotics in biodegradable NPs has been shown to provide effective therapy and reduced toxicity against M. tuberculosis in different mammalian models, when compared to conventional free drug administration. Here, we evaluate the localization, therapeutic efficacy and toxic effects of polymeric micellar NPs encapsulating a promising but highly hydrophobic and toxic antitubercular drug bedaquiline (BQ) in zebrafish embryos infected with Mycobacterium marinum. Our study shows that the NP formulation of BQ improves survival and reduces bacterial burden in the infected embryos after treatment when compared to its free form. The intravenously injected BQ NPs have short circulation times due to their rapid and efficient uptake into the endothelial cells, as observed by correlative light and electron microscopy (CLEM).

Idioma: Inglés

DOI: 10.1039/d2bm01835g

Año: 2023

Publicado en: Biomaterials Science 11, 6 (2023), 2103-2114
ISSN: 2047-4830

Factor impacto JCR: 5.8 (2023)

Categ. JCR: MATERIALS SCIENCE, BIOMATERIALS rank: 12 / 53 = 0.226 (2023) - Q1 - T1

Factor impacto SCIMAGO: 1.206 - Materials Science (miscellaneous) (Q1) - Biomedical Engineering (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/E15-20R
Financiación: info:eu-repo/grantAgreement/ES/MEC/FPU2016-02456
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-109333RB-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)