The achievement of parasitological cure of dogs with visceral leishmaniasis (VL) remains a great challenge,\nsince dogs act as main reservoir for transmission of Leishmania infantum to humans and respond poorly to\nconventional drugs including pentavalent antimonials. Liposome-encapsulated antimonials are hundreds of\ntimes more effective than the free drugs against VL based on parasite suppression in the liver. However,\ncomplete parasite elimination in dogs seems to depend on the ability of liposomes to reach less accessible\ninfection sites such as the bone marrow and the skin. Recently, the reduction of liposome size from 1200- to\n400-nm diameter was found to improve the targeting of Sb to the bone marrow of dogs with VL. In the present\n \n\n\n\n \n\nvesicle diameter from 400- to 175-nm on the pharmacokinetics of Sb\nin dogs with VL and on the distribution of Sb in the liver, spleen and bone marrow were investigated. For this\npurpose, two liposome formulations of meglumine antimoniate with the same lipid composition but different\nmean hydrodynamic diameters were prepared. The formulations were given to mongrel dogs with VL as a\nsingle intravenous bolus injection and Sb concentrations were determined by graphite furnace atomic absorption\nspectroscopy. Surprisingly, much more prolonged blood levels of Sb were achieved from small size (175 nm)\nthan medium size (400 nm) liposomes. Small size vesicles were also less effective than medium size ones\nin targeting Sb to the liver. On the other hand, similar Sb concentrations were achieved in both spleen and\nbone marrow. In conclusion, the prolonged blood circulation time of liposomes with 175-nm diameter makes this\nnanosystem suitable for passive drug targeting to the less accessible infection sites in dogs with VL.
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