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Tytuł:
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Higher oral efficacy of ravuconazole in self-nanoemulsifying systems in shorter treatment in experimental chagas disease.
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Autorzy:
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Spósito PÁ; Laboratory of Pharmaceutics and Nanotechnology (LDGNano), Pharmacy School, Federal University of Ouro Preto, Minas Gerais, 35400-000, Brazil.
Mazzeti AL; Laboratory of Pharmaceutics and Nanotechnology (LDGNano), Pharmacy School, Federal University of Ouro Preto, Minas Gerais, 35400-000, Brazil; Laboratory of Cellular Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.
de Castro KCMP; Laboratory of Pharmaceutics and Nanotechnology (LDGNano), Pharmacy School, Federal University of Ouro Preto, Minas Gerais, 35400-000, Brazil; Laboratory of Parasitic Diseases, School of Medicine, Federal University of Ouro Preto, Minas Gerais, Brazil.
Mendes PF; Laboratory of Pharmaceutics and Nanotechnology (LDGNano), Pharmacy School, Federal University of Ouro Preto, Minas Gerais, 35400-000, Brazil.
Urbina JA; Venezuelan Institute for Scientific Research, Caracas, 1020A, Venezuela.
Bahia MT; Laboratory of Parasitic Diseases, School of Medicine, Federal University of Ouro Preto, Minas Gerais, Brazil.
Mosqueira VCF; Laboratory of Pharmaceutics and Nanotechnology (LDGNano), Pharmacy School, Federal University of Ouro Preto, Minas Gerais, 35400-000, Brazil. Electronic address: .
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Źródło:
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Experimental parasitology [Exp Parasitol] 2021 Sep; Vol. 228, pp. 108142. Date of Electronic Publication: 2021 Aug 08.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Orlando, FL : Academic Press
Original Publication: New York.
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MeSH Terms:
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Chagas Disease/*drug therapy
Thiazoles/*administration & dosage
Triazoles/*administration & dosage
Trypanosoma cruzi/*drug effects
Animals ; Chagas Disease/parasitology ; Emulsions ; Female ; Hep G2 Cells ; Humans ; Inhibitory Concentration 50 ; Mice ; Myocytes, Cardiac ; Nanostructures ; Rats ; Thiazoles/pharmacology ; Thiazoles/therapeutic use ; Thiazoles/toxicity ; Triazoles/pharmacology ; Triazoles/therapeutic use ; Triazoles/toxicity
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Contributed Indexing:
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Keywords: Colombian strain; Efficacy; Ravuconazole; Self-nanoemulsifying drug delivery system; Toxicity; Trypanosoma cruzi; Y strain
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Substance Nomenclature:
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0 (Emulsions)
0 (Thiazoles)
0 (Triazoles)
95YH599JWV (ER 30346)
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Entry Date(s):
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Date Created: 20210810 Date Completed: 20210826 Latest Revision: 20210826
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Update Code:
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20240105
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DOI:
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10.1016/j.exppara.2021.108142
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PMID:
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34375652
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We investigated the in vitro activity and selectivity, and in vivo efficacy of ravuconazole (RAV) in self-nanoemulsifying delivery system (SNEDDS) against Trypanosoma cruzi. Novel formulations of this poorly soluble C14-α-demethylase inhibitor may improve its efficacy in the experimental treatment. In vitro activity was determined in infected cardiomyocytes and efficacy in vivo evaluated in terms of parasitological cure induced in Y and Colombian strains of T. cruzi-infected mice. In vitro RAV-SNEDDS exhibited significantly higher potency of 1.9-fold at the IC 50 level and 2-fold at IC 90 level than free-RAV. No difference in activity with Colombian strain was observed in vitro. Oral treatment with a daily dose of 20 mg/kg for 30 days resulted in 70% of cure for RAV-SNEDDS versus 40% for free-RAV and 50% for 100 mg/kg benznidazole in acute infection (T. cruzi Y strain). Long-term treatment efficacy (40 days) was able to cure 100% of Y strain-infected animals with both RAV preparations. Longer treatment time was also efficient to increase the cure rate with benznidazole (Y and Colombian strains). RAV-SNEDDS shows greater efficacy in a shorter time treatment regimen, it is safe and could be a promising formulation to be evaluated in other pre-clinical models to treat T. cruzi and fungi infections.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
