Please use this identifier to cite or link to this item: http://hdl.handle.net/10637/13019

Ultradeformable lipid vesicles localize Amphotericin B in the dermis for the treatment of infectious skin diseases

Title: Ultradeformable lipid vesicles localize Amphotericin B in the dermis for the treatment of infectious skin diseases
Authors : Fernández García, Raquel
Statts, Larry
Jesus, Jéssica A. de
Dea Ayuela, María Auxiliadora
Bautista, Liliana
Simao, Rúben
Keywords: Piel - Enfermedades.Anfotericina B - Uso terapéutico.Skin - Diseases.Zoonosis.Leishmaniasis.Zoonoses.Amphotericin B - Therapeutical use.
Publisher: American Chemical Society.
Citation: Fernández-García, R., Statts, L., Jesus, J.A. de, Dea-Ayuela, M.A., Bautista, L., Simão, R. et al. (2020). Ultradeformable lipid vesicles localize Amphotericin B in the dermis for the treatment of infectious skin diseases. ACS Infectious Diseases, vol. 6, i. 10 (18 aug.), pp. 2647-2660. DOI: https://doi.org/10.1021/acsinfecdis.0c00293
Abstract: Cutaneous fungal and parasitic diseases remain challenging to treat, as available therapies are unable to permeate the skin barrier. Thus, treatment options rely on systemic therapy, which fail to produce high drug local concentrations but can lead to significant systemic toxicity. Amphotericin B (AmB) is highly efficacious in the treatment of both fungal and parasitic diseases such as cutaneous leishmaniasis, but is only reserved for parenteral administration in patients with severe pathophysiology. Here, we have designed and optimised AmB-transfersomes [93.5 % encapsulation efficiency, size of 150 nm, and good colloidal stability (-35.02 mV)] that can remain physicochemically stable (>90 % drug content) at room temperature and 4 °C over 6 months when lyophilised and stored under desiccated conditions. AmBtransfersomes possessed good permeability across mouse skin (4.91 ± 0.41 μg/cm2/h) and 10-fold higher permeability across synthetic Strat-M® membranes. In vivo studies after a single topical application in mice showed permeability and accumulation within the dermis (>25 μg AmB /g skin at 6 h post-administration) indicating the delivery of therapeutic amounts of AmB for mycoses and cutaneous leishmaniasis, while a single daily administration in Leishmania (Leishmania) amazonensis infected mice over 10 days resulted in excellent efficacy (98 % reduction in Leishmania parasites). Combining the application of AmB-transfersomes with metallic microneedles in vivo increased levels in the SC and dermis but is unlikely to elicit transdermal levels. In conclusion, AmB-transfersomes are promising and stable topical nanomedicines that can be readily translated for parasitic and fungal infectious diseases.
Description: Este artículo se encuentra disponible en la siguiente URL: https://pubs.acs.org/doi/10.1021/acsinfecdis.0c00293
Nota de Fondos: Esta versión preprint del artículo se encuentra a texto completo en el CEU Repositorio Institucional.
En esta investigación también participan: Francisco Bolás-Fernández, Maria Paloma Ballesteros, Marcia Dalastra Laurenti, Luiz F. D. Passero, Aikaterini Lalatsa y Dolores R. Serrano.
This is the pre-peer reviewed version of the following article: Fernández-García, R., Statts, L., Jesús, J.A., Dea-Ayuela, M.A., Bautista, L., Simao, R. et al. (2020). Ultradeformable lipid vesicles localize Amphotericin B in the dermis for the treatment of infectious skin diseases. ACS Infectious Diseases, vol. 6, i. 10 (18 aug.), pp. 2647-2660, which has been published in final form at https://doi.org/10.1021/acsinfecdis.0c00293
Este es el pre-print del siguiente artículo: Fernández-García, R., Statts, L., Jesús, J.A., Dea-Ayuela, M.A., Bautista, L., Simao, R. et al. (2020). Ultradeformable lipid vesicles localize Amphotericin B in the dermis for the treatment of infectious skin diseases. ACS Infectious Diseases, vol. 6, i. 10 (18 aug.), pp. 2647-2660, que se ha publicado de forma definitiva en https://doi.org/10.1021/acsinfecdis.0c00293
URI: http://hdl.handle.net/10637/13019
Rights : http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
ISSN: 2373-8227 (Electrónico).
Issue Date: 18-Aug-2020
Center : Universidad Cardenal Herrera-CEU
Appears in Collections:Dpto. Farmacia





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