Pyrimethamine-loaded lipid-core nanocapsules to improve drug efficacy for the treatment of toxoplasmosis
We propose an innovative product based on the nanoencapsulation of pyrimethamine (PYR), aiming an improvement of drug efficacy for the treatment of toxoplasmosis. The in vitro cytotoxicity effect of encapsulated PYR and PYR-colloidal suspension was concomitantly evaluated against LLC-MK2 lineage and mouse peritoneal macrophage showing that the cells had similar tolerance for both PYR encapsulated or in the aqueous suspension. CF1 mice acutely infected with tachyzoites of Toxoplasma gondii RH strain treated with different doses (5.0–10 mg/kg/day) of PYR-nanocapsules had survival rate higher than the animals treated with the same doses of non-encapsulated PYR. Thus, encapsulation of PYR improved the efficacy of this drug against an acute model of toxoplasmosis in mice and can be considered an alternative for reducing the dose of PYR, which, in turn, could also reduce the side effects associated to the treatment.
KeywordsEncapsulation Efficiency Toxoplasmosis Polysorbate Pyrimethamine Atovaquone
The authors thank Mr. Helcio Evangelista da Silva for technical assistance with animal care, Dr. Daniel Gonçalves for technical assistance with FESEM and Dr. Eduardo José Torres and Dr. Kildare Miranda for helpful discussions. The authors would like to thank Perstorp for kindly providing the CAPA® 6500 product. This work was supported by Rede Nanobiotec-Brazil CAPES, Grants CNPq/MCT, and Fellows CAPES. Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Programa de Núcleos de Excelência-Pronex-FAPERJ-CNPq and Pronex FAPERGS-CNPq (#10/0048-4).
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