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Efficacy and non-toxicity of ciclopirox olamine-loaded liposomes against Cryptococcus neoformans clinical isolates

  • Biotechnology and Industrial Microbiology - Research Paper
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Abstract

The aim of this study was to evaluate the efficacy and non-toxicity of ciclopirox olamine-loaded liposomes against Cryptococcus neoformans clinical isolates. Initially, 24–1 fractional experimental design was carried out to obtain an optimized formulation of liposomes containing CPO (CPO-LipoC), which were then used to prepare stealth liposomes (CPO-LipoS). Liposomal formulations were characterized by their mean size diameter, polydispersity index (PDI), and drug encapsulation efficiency (EE%). Immunosuppressed mice were exposed to CPO-LipoS at 0.5 mg/kg/day for 14 days to verify possible histopathological alterations in the liver and kidneys. Immunosuppressed mice infected with C. neoformans were treated with CPO-LipoS at 0.5 mg/kg/day for 14 days to quantify the fungal burden in spleen, liver, lungs, and brain. CPO-LipoS presented a mean size diameter, PDI, and EE% of 101.4 ± 0.7 nm, 0.307, and 96.4 ± 0.9%, respectively. CPO-LipoS was non-toxic for the liver and kidneys of immunosuppressed mice. At the survival curve, all infected animals submitted to treatment with CPO-LipoS survived until the end of the experiment. Treatment with CPO-LipoS reduced C. neoformans cells in the spleen (59.3 ± 3.4%), liver (75.0 ± 3.6%), lungs (75.7 ± 6.7%), and brain (54.2 ± 3.2%). CPO-LipoS exhibit antifungal activity against C. neoformans, and the encapsulation of CPO into stealth liposomes allows its use as a systemic drug for treating cryptococcosis.

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Acknowledgements

POK thanks the Brazilian National Council for Scientific and Technological Development (CNPq) for a PhD scholarship.

Funding

The current study was supported by the CNPq [n. 474777/2013–8, n. 484574/2011-6 and n. 477215/2013-0] and by the Science and Technology Support Foundation of Pernambuco State (FACEPE) [APQ-0814–4.03/17 and APQ-0287-4.03/22].

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Authors and Affiliations

  1. Biosciences Center, Laboratory of Medical Mycology, Federal University of Pernambuco (UFPE), Av Reitor Joaquim Amazonas, S/N, Cidade Universitária, Recife, PE, 50740-570, Brazil

    Patrícia de Oliveira Kocerginsky, Reginaldo Gonçalves de Lima-Neto & Rejane Pereira Neves

  2. Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, 50670-901, Brazil

    Patrícia de Oliveira Kocerginsky, Pedro Henrique dos Santos Soares, Hannah Ferreira Soares Lyra, Pabyton Gonçalves Cadena, Sérgio Dias Costa-Júnior, Isabella Macário Ferro Cavalcanti & Nereide Stela Santos-Magalhães

  3. Department of Animal Morphology and Physiology, Federal Rural University of Pernambuco (UFRPE), Rua Dom Manoel de Medeiros, S/N, Dois Irmãos, Recife, PE, 52171-900, Brazil

    Pabyton Gonçalves Cadena

  4. Health Sciences Center, Department of Tropical Medicine, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, 50670-901, Brazil

    Reginaldo Gonçalves de Lima-Neto

  5. Center for Health Sciences, Department of Pathology, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, 50670-901, Brazil

    Nicodemos Teles Pontes-Filho

  6. Department of Biology, Federal Rural University of Pernambuco (UFRPE), Rua Dom Manoel de Medeiros, 401, Dois Irmãos, Recife, PE, 52171-900, Brazil

    José Vitor Moreira Lima-Filho

  7. Academic Center of Vitória (CAV), Laboratory of Microbiology and Immunology, Vitória de Santo Antão, Federal University of Pernambuco (UFPE), Rua Alto Do Reservatório, S/N, Vitória de Santo Antão, PE, Brazil

    Isabella Macário Ferro Cavalcanti

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  1. Patrícia de Oliveira Kocerginsky
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  2. Pedro Henrique dos Santos Soares
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Contributions

POK designed the project, executed the laboratorial methodology, analyzed the data, and wrote the article. PHSS, HFSL, SDCJ, and PGC assisted in the laboratory experiments, data analysis, and writing the manuscript. RGLN and RPN performed analysis of antifungal activity. NTPF and JVMLF contributed to in vivo studies. IMFC and NSSM supervised the laboratory experiments and contributed to the critic evaluation of the manuscript. All the authors have read the manuscript and approved its submission.

Corresponding authors

Correspondence to Isabella Macário Ferro Cavalcanti or Nereide Stela Santos-Magalhães.

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de Oliveira Kocerginsky, P., dos Santos Soares, P.H., Lyra, H.F.S. et al. Efficacy and non-toxicity of ciclopirox olamine-loaded liposomes against Cryptococcus neoformans clinical isolates. Braz J Microbiol 54, 1513–1521 (2023). https://doi.org/10.1007/s42770-023-01071-6

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