201. Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis.
- Author
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Spadari CC, de Bastiani FWMDS, Lopes LB, and Ishida K
- Subjects
- Animals, Antifungal Agents pharmacology, Antifungal Agents therapeutic use, Candida albicans drug effects, Candidiasis microbiology, Cryptococcosis microbiology, Drug Liberation, Larva drug effects, Microbial Sensitivity Tests, Nanoparticles ultrastructure, Phosphorylcholine pharmacology, Phosphorylcholine therapeutic use, Phosphorylcholine toxicity, Sheep, Alginates chemistry, Candidiasis drug therapy, Cryptococcosis drug therapy, Drug Delivery Systems, Nanoparticles chemistry, Phosphorylcholine analogs & derivatives
- 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 ., Competing Interests: Dr Cristina de Castro Spadari and Dr Fernanda Walt Mendes da Silva de Bastiani were participants of the fellowship program from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Dr Cristina de Castro Spadari reports a patent BR 10 2017 018011 5 pending; Dr Fernanda Walt Mendes da Silva de Bastiani reports a patent BR 10 2017 018011 5 pending; Dr Luciana Biagini Lopes reports a patent BR 10 2017 018011 5 pending and Dr Kelly Ishida reports a patent BR 10 2017 018011 5 pending. Dr Luciana Biagini Lopes reports grants from São Paulo Research Foundation, during the conduct of the study and non-financial support from Abitech, outside the submitted work. The authors report no other conflicts of interest in this work.
- Published
- 2019
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