Prolonged Blood Circulation Time of Antimony in Dogs with Visceral Leishmaniasis from Liposomes with 175-nm DiameterErly Guilherme Azevedo1, Raul Rio Ribeiro2, Cláudio dos Santos Ferreira3, Sydnei Magno da Silva4, Dante Aligheiri Schettini5, Marilene Suzan Marques Michalick4, Cynthia Demicheli6 and Frédéric Frézard1*
2Department of Veterinary Medicine, Center for Agricultural Sciences, Environmental and Biological Sciences, Federal University of Bahia Recôncavo, Campus of Cruz das Almas, Centre, 44380-000 Cruz das Almas, Bahia, Brazil
- *Corresponding Author:
- Frédéric Frézard
Department of Physiology and Biophysics
Institute of Biological Sciences
Federal University of Minas Gerais, Av Antonio Carlos 6627
Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
Tel :+55 31 34092940
Fax: +55 31 34092924
E-mail: [email protected]
Received date: November 21, 2011; Accepted date: December 08, 2011; Published date: December 13, 2011
Citation: Azevedo EG, Ribeiro RR, Ferreira CS, da Silva SM, Schettini DA, et al. (2011) Prolonged Blood Circulation Time of Antimony in Dogs with Visceral Leishmaniasis from Liposomes with 175-nm Diameter. J Nanomedic Biotherapeu Discover 1:101. doi:10.4172/2155-983X.1000101
Copyright: © 2011 Azevedo EG, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The achievement of parasitological cure of dogs with visceral Leishmaniasis (VL) remains a great challenge, since dogs act as main reservoir for transmission of Leishmania infantum to humans and respond poorly to conventional drugs including pentavalent antimonials. Liposome-encapsulated antimonials are hundreds of times more effective than the free drugs against VL based on parasite suppression in the liver. However, complete parasite elimination in dogs seems to depend on the ability of liposomes to reach less accessible infection sites such as the bone marrow and the skin. Recently, the reduction of liposome size from 1200- to 400-nm diameter was found to improve the targeting of Sb to the bone marrow of dogs with VL. In the present work, the influence of further reduction of vesicle diameter from 400- to 175-nm on the pharmacokinetics of Sb in dogs with VL and on the distribution of Sb in the liver, spleen and bone marrow were investigated. For this purpose, two liposome formulations of meglumine antimoniate with the same lipid composition but different mean hydrodynamic diameters were prepared. The formulations were given to mongrel dogs with VL as a single intravenous bolus injection and Sb concentrations were determined by graphite furnace atomic absorption spectroscopy. Surprisingly, much more prolonged blood levels of Sb were achieved from small size (175 nm) than medium size (400 nm) liposomes. Small size vesicles were also less effective than medium size ones in targeting Sb to the liver. On the other hand, similar Sb concentrations were achieved in both spleen and bone marrow. In conclusion, the prolonged blood circulation time of liposomes with 175-nm diameter makes this nanosystem suitable for passive drug targeting to the less accessible infection sites in dogs with VL.