Abstract
Chagas disease (CD), present in Latin America, is neglected and autochthone in other Continents [1]. Objetive: (i) evaluate the pharmacokinetic of LYC, a sesquiterpene lactone extracted from Lychnophora trichocarpha and LYC-NC formulated in polymeric nanocapsules (NC) and (ii) its efficacy in Swiss mice infected with Trypanosoma cruzi strains of different patterns of drugs resistance. NC was produced [2] at different concentrations of LYC and LYC-NCs were fully characterized, rending high percentages of encapsulation [3,4] and showing high stability. A new fast and precise bioanalytical method was developed (HPLC-UV detection), validated following FDA and National Agency of Sanitary Vigilance/Brazil guidelines [5] and further applied to LYC pharmacokinetic evaluation. It was observed an increasing in AUC (14 fold) and t1/2 (2,4 fold) and reduction of the Clearance (124 fold) of LYC when associated to PLA-PEG-NC x PLC-NC. The efficacy of free LYC, LYC-NC, BZ and controls was studied in mice inoculated with 1.0 × 104 trypomastigotes (acute phase) or 500 (chronic phase) of the CL, Y, Colombiana, VL10 T. cruzi strains. The cure rate in mice infected with all strains, acute and chronic phases, treated by IV/oral routes decreases in the following order: LYC-PLA-PEG-NC>LYC-PCL-NC>LYC free>BZ and was 0% for all controls. Cure rate of 88% was found with LYC-PLAPEG-NC treatment by oral route for resistant T. cruzi strain in chronic model (VL10 strain). This study is pioneer in the demonstration of better efficacy of LYC in vivo, when associated with NC, compared with BZ treatment of experimental CD, in both phases of infection with T. cruzi strains totally resistant to BZ/Nifurtimox. Furthermore, PLA-PEG-NC improved the pharmacokinetic parameters of LYC, increasing its plasma AUC and mean residence time, which contributes to the improvement of the efficacy in mice and showing the great potential of LYC for further clinical studies of CD treatment.
Published Version
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