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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Spadari, Cristina de Castro [1] ; Mendes da Silva de Bastiani, Fernanda Walt [1] ; Lopes, Luciana Biagini [2] ; Ishida, Kelly [1]
Total Authors: 4
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: INTERNATIONAL JOURNAL OF NANOMEDICINE; v. 14, p. 5187-5199, 2019.
Web of Science Citations: 2
Abstract

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)

FAPESP's process: 13/16617-7 - Nanostructured systems for topical delivery and co-localization of chemopreventive and chemoterapeutic agents in the skin and breast tissue
Grantee:Luciana Biagini Lopes
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 18/12149-2 - Nanoparticles as carriers of miltefosine for treatment of cryptococcal meningitis.
Grantee:Cristina de Castro Spadari
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/07993-0 - ENCAPSULATION OF MILTEFOSINE INTO MICROPARTICLES OF ALGINATE AND EVALUATION OF EFFECTS "IN VITRO" AND "IN VIVO" ON MURINE MODEL OF PULMONARY CRYPTOCOCCOSIS
Grantee:Kelly Ishida
Support Opportunities: Regular Research Grants