Increased Body Exposure to New Anti-Trypanosomal Through Nanoencapsulation.

Autor:	Tupinambá Branquinho R; Nucleus of Research in Biological Sciences (NUPEB), Biological Sciences Post-Graduation Program, Federal University of Ouro Preto, Minas Gerais, Brazil.; Laboratory of Pharmaceutics and Nanobiotechnology (LDGNano) - Pharmacy School, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Post-graduation Program in Pharmaceutical Sciences (CIPHARMA), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Pound-Lana G; Laboratory of Pharmaceutics and Nanobiotechnology (LDGNano) - Pharmacy School, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Post-graduation Program in Pharmaceutical Sciences (CIPHARMA), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Marques Milagre M; Post-graduation Program in Pharmaceutical Sciences (CIPHARMA), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Saúde-Guimarães DA; Post-graduation Program in Pharmaceutical Sciences (CIPHARMA), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Vilela JMC; Technological Center - CETEC SENAI - Minas Gerais Regional Department - Belo Horizonte, Minas Gerais, Brazil., Spangler Andrade M; Technological Center - CETEC SENAI - Minas Gerais Regional Department - Belo Horizonte, Minas Gerais, Brazil., de Lana M; Nucleus of Research in Biological Sciences (NUPEB), Biological Sciences Post-Graduation Program, Federal University of Ouro Preto, Minas Gerais, Brazil.; Post-graduation Program in Pharmaceutical Sciences (CIPHARMA), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Mosqueira VCF; Nucleus of Research in Biological Sciences (NUPEB), Biological Sciences Post-Graduation Program, Federal University of Ouro Preto, Minas Gerais, Brazil. mosqueira@ef.ufop.br.; Laboratory of Pharmaceutics and Nanobiotechnology (LDGNano) - Pharmacy School, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil. mosqueira@ef.ufop.br.; Post-graduation Program in Pharmaceutical Sciences (CIPHARMA), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil. mosqueira@ef.ufop.br.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2017 Aug 16; Vol. 7 (1), pp. 8429. Date of Electronic Publication: 2017 Aug 16.
DOI:	10.1038/s41598-017-08469-x
Abstrakt:	Lychnopholide, a lipophilic sesquiterpene lactone, is efficacious in mice at the acute and chronic phases of Chagas disease. Conventional poly-ε-caprolactone (PCL) and long-circulating poly(D,L-lactide)-block-polyethylene glycol (PLA-PEG) nanocapsules containing lychnopholide were developed and characterized. Lychnopholide presented high association efficiency (>90%) with the nanocapsules. A new, fast and simple HPLC-UV-based bioanalytical method was developed, validated in mouse plasma and applied to lychnopholide quantification in in vitro release kinetics and pharmacokinetics. The nanocapsules had mean hydrodynamic diameters in the range of 100-250 nm, negative zeta potentials (-30 mV to -57 mV), with good physical stability under storage. Atomic force microscopy morphological analysis revealed spherical monodispersed particles and the absence of lychnopholide crystallization or aggregation. Association of lychnopholide to PLA-PEG nanocapsules resulted in a 16-fold increase in body exposure, a 26-fold increase in plasma half-life and a dramatic reduction of the lychnopholide plasma clearance (17-fold) in comparison with free lychnopholide. The improved pharmacokinetic profile of lychnopholide in long-circulating nanocapsules is in agreement with the previously reported improved efficacy observed in Trypanosoma cruzi-infected mice. The present lychnopholide intravenous dosage form showed great potential for further pre-clinical and clinical studies in Chagas disease and cancer therapies.
Databáze:	MEDLINE
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