Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis

Cristina de Castro Spadari,*,1 Fernanda Walt Mendes da Silva de Bastiani,*,1 Luciana Biagini Lopes,2 Kelly Ishida11Laboratory of Antifungal Chemotherapy, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;...

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Autores principales:	Spadari CC, de Bastiani FWMS, Lopes LB, Ishida K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	nanocarriers antifungal drug delivery Galleria mellonella invasive fungal infection. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bfee00b3dffa4e8eb6e432e24b34f458
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spelling	oai:doaj.org-article:bfee00b3dffa4e8eb6e432e24b34f4582021-12-02T11:29:56ZAlginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis1178-2013https://doaj.org/article/bfee00b3dffa4e8eb6e432e24b34f4582019-07-01T00:00:00Zhttps://www.dovepress.com/alginate-nanoparticles-as-non-toxic-delivery-system-for-miltefosine-in-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Cristina de Castro Spadari,,1 Fernanda Walt Mendes da Silva de Bastiani,,1 Luciana Biagini Lopes,2 Kelly Ishida11Laboratory of Antifungal Chemotherapy, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; 2Laboratory of Nanomedicine and Drug Delivery Systems, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil*These authors contributed equally to this workIntroduction and objective: Previous studies indicate that miltefosine (MFS) may be an alternative as an antifungal agent; however, it presents several adverse effects. Thus, the aim of this study was to produce miltefosine-loaded alginate nanoparticles (MFS.Alg) for toxicity reduction to be used as an alternative for the treatment of cryptococcosis and candidiasis.Methods: Alginate nanoparticles were produced using the external emulsification/gelation method, and their physicochemical and morphological characteristics were analyzed. MFS encapsulation efficiency, release assay and toxicity on red blood cells and on Galleria mellonella larvae were assessed. The antifungal activity was evaluated using in vitro and in vivo larval models of G. mellonella infected with Candida albicans (SC5314 and IAL-40), Cryptococcus neoformans H99 and Cryptococcus gattii ATCC 56990. The treatment efficacy was evaluated by survival curve, colony forming unit (CFU) counting and histopathological analysis.Results: MFS.Alg nanoparticles presented a mean size of 279.1±56.7 nm, a polydispersity index of 0.42±0.15 and a zeta potential of −39.7±5.2 mV. The encapsulation efficiency of MFS was 81.70±6.64%, and its release from the nanoparticles occurred in a sustained manner. MFS in alginate nanoparticles presented no hemolytic effect and no toxicity in G. mellonella larvae. Treatment with MFS.Alg extended the survival time of larvae infected with C. albicans and C. gattii. In addition, the fungal burden reduction was confirmed by CFU and histopathological data for all groups treated with 200 mg/Kg of MFS.Alg.Conclusion: These results support the use of alginate-based drug delivery systems as carriers for MFS for drug toxicity reduction and control of the fungal infection in the in vivo model of G. mellonella.Keywords: nanocarriers, antifungal, drug delivery, Galleria mellonella, invasive fungal infectionSpadari CCde Bastiani FWMSLopes LBIshida KDove Medical Pressarticlenanocarriersantifungaldrug deliveryGalleria mellonellainvasive fungal infection.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5187-5199 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanocarriers antifungal drug delivery Galleria mellonella invasive fungal infection. Medicine (General) R5-920
spellingShingle	nanocarriers antifungal drug delivery Galleria mellonella invasive fungal infection. Medicine (General) R5-920 Spadari CC de Bastiani FWMS Lopes LB Ishida K Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis
description	Cristina de Castro Spadari,,1 Fernanda Walt Mendes da Silva de Bastiani,,1 Luciana Biagini Lopes,2 Kelly Ishida11Laboratory of Antifungal Chemotherapy, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; 2Laboratory of Nanomedicine and Drug Delivery Systems, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil*These authors contributed equally to this workIntroduction and objective: Previous studies indicate that miltefosine (MFS) may be an alternative as an antifungal agent; however, it presents several adverse effects. Thus, the aim of this study was to produce miltefosine-loaded alginate nanoparticles (MFS.Alg) for toxicity reduction to be used as an alternative for the treatment of cryptococcosis and candidiasis.Methods: Alginate nanoparticles were produced using the external emulsification/gelation method, and their physicochemical and morphological characteristics were analyzed. MFS encapsulation efficiency, release assay and toxicity on red blood cells and on Galleria mellonella larvae were assessed. The antifungal activity was evaluated using in vitro and in vivo larval models of G. mellonella infected with Candida albicans (SC5314 and IAL-40), Cryptococcus neoformans H99 and Cryptococcus gattii ATCC 56990. The treatment efficacy was evaluated by survival curve, colony forming unit (CFU) counting and histopathological analysis.Results: MFS.Alg nanoparticles presented a mean size of 279.1±56.7 nm, a polydispersity index of 0.42±0.15 and a zeta potential of −39.7±5.2 mV. The encapsulation efficiency of MFS was 81.70±6.64%, and its release from the nanoparticles occurred in a sustained manner. MFS in alginate nanoparticles presented no hemolytic effect and no toxicity in G. mellonella larvae. Treatment with MFS.Alg extended the survival time of larvae infected with C. albicans and C. gattii. In addition, the fungal burden reduction was confirmed by CFU and histopathological data for all groups treated with 200 mg/Kg of MFS.Alg.Conclusion: These results support the use of alginate-based drug delivery systems as carriers for MFS for drug toxicity reduction and control of the fungal infection in the in vivo model of G. mellonella.Keywords: nanocarriers, antifungal, drug delivery, Galleria mellonella, invasive fungal infection
format	article
author	Spadari CC de Bastiani FWMS Lopes LB Ishida K
author_facet	Spadari CC de Bastiani FWMS Lopes LB Ishida K
author_sort	Spadari CC
title	Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis
title_short	Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis
title_full	Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis
title_fullStr	Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis
title_full_unstemmed	Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis
title_sort	alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/bfee00b3dffa4e8eb6e432e24b34f458
work_keys_str_mv	AT spadaricc alginatenanoparticlesasnontoxicdeliverysystemformiltefosineinthetreatmentofcandidiasisandcryptococcosis AT debastianifwms alginatenanoparticlesasnontoxicdeliverysystemformiltefosineinthetreatmentofcandidiasisandcryptococcosis AT lopeslb alginatenanoparticlesasnontoxicdeliverysystemformiltefosineinthetreatmentofcandidiasisandcryptococcosis AT ishidak alginatenanoparticlesasnontoxicdeliverysystemformiltefosineinthetreatmentofcandidiasisandcryptococcosis
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Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis

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