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In vitro evaluation of the effectiveness of new water-stable cationic carbosilane dendrimers against Acanthamoeba castellanii UAH-T17c3 trophozoites

Abstract

Acanthamoeba is one of the most common free-living amoebas which is widespread in the environment and can infect humans, causing diseases such as keratitis and encephalitis. In this paper we examine for the first time the amebicidal activity of the family of cationic dendrimers nG-[Si{(CH2)3N+(Me)(Et)(CH2)2NMe3 +}2I] x (where n denotes the generations: zero (n = 0, x = 1), first (n = 1, x = 4), and second (n = 2, x = 8); for simplicity, they were named as 0G-CNN2, 1G-CNN8, and 2G-CNN16, respectively) against Acanthamoeba castellanii UAH-T17c3 trophozoites. In order to test the amebicidal activity, we cultured the strain A. castellanii UAH-T17c3 in PYG-Bactocasitone medium and later, we treated it with different concentrations of these dendrimers and monitored the effects and damage by optical count, flow cytometry, and scanning electron microscopy. The results showed that all the nanosystems assayed had a strong amebicidal activity. The dendrimer 1G-CNN8 was the most effective against the amoeba. In the morphology of treated throphozoites of A. castellanii UAH-T17c3 analyzed by light and scanning electron microscopy techniques, morphological changes were evident in amoeba cells, such as loss of pseudopodia, ectoplasm increase, roundness, and cellular lysis. Furthermore, flow cytometry results showed alterations in cell granularity, which was dose–time dependent. In conclusion, this family of cationic carbosilane dendrimers has a strong amebicidal activity against the trophozoites of A. castellanii UAH-T17c3 in vitro. They could potentially become new agents significant to the development of new amebicidal compounds for prevention and therapy of Acanthamoeba infections.

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Acknowledgments

We wish to thank Mrs. Isabel Trabado for the technical assistance from Cell Culture Unit (CAI Medicina y Biología de la Universidad de Alcala), Mr. Antonio Priego and Mr. Jose Antonio Pérez for scanning electron microscopy assistance (CAI Medicina y Biología de la Universidad de Alcala), Mr. Angel Pueblas for the photography support from the Photography Unit (CAI Medicina y Biología de la Universidad de Alcala), and Prof. Angel Criado and Andreas Britz for language assistance.

This work was supported by the grants provided by a fellowship from the Ministerio de Educación y Ciencia (FPU ref. AP2010-1471), and the Consejería de Educación de la Comunidad de Madrid and Fondo Social Europeo (F.S.E.) for S.G.G. Fondos de Investigación Sanitaria (FIS) (PI080222), CTQ2011-23245 (MEyC), Consorcium NANODENDMED ref. S2011/BMD-2351 (CAM), and CIBER-BBN to U.A. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.

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Correspondence to J. Pérez-Serrano.

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Heredero-Bermejo, I., Copa-Patiño, J.L., Soliveri, J. et al. In vitro evaluation of the effectiveness of new water-stable cationic carbosilane dendrimers against Acanthamoeba castellanii UAH-T17c3 trophozoites. Parasitol Res 112, 961–969 (2013). https://doi.org/10.1007/s00436-012-3216-z

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  • DOI: https://doi.org/10.1007/s00436-012-3216-z

Keywords

  • Viability Percentage
  • Ciclopirox
  • Flow Cytometry Result
  • Cell Granularity
  • Dendrimer Generation