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

Autor(es)

Spadari, Cristina de Castro ^[1] ; Mendes da Silva de Bastiani, Fernanda Walt ^[1] ; Lopes, Luciana Biagini ^[2] ; Ishida, Kelly ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Lab Antifungal Chemotherapy, Prof Lineu Prestes Ave 1374, ICB 2, Lab 150, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Lab Nanomed & Drug Delivery Syst, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF NANOMEDICINE; v. 14, p. 5187-5199, 2019.
• Citações Web of Science: 2

Resumo

Introduction 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. (AU)

• Processo FAPESP: 13/16617-7 - Sistemas nanoestruturados tópicos para co-localização de agentes quimioterápicos e quimiopreventivos na pele e mama
• Beneficiário: Luciana Biagini Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 18/12149-2 - Nanopartículas como carreadores de miltefosina para tratamento de meningite criptocócica.
• Beneficiário: Cristina de Castro Spadari
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/07993-0 - Encapsulamento da miltefosina em micropartículas de alginato e avaliação dos efeitos "in vitro" e "in vivo" em modelo murino de criptococose pulmonar
• Beneficiário: Kelly Ishida
• Modalidade de apoio: Auxílio à Pesquisa - Regular