Pentavalent antimonials: New perspectives for old drugs

Molecules

Volumn 14, Issue 7, 2009, Pages 2317-2336

  Frézard, Frédéric ^a   Demicheli, Cynthia ^a   Ribeiro, Raul R ^a  

^a FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

Author keywords

Cyclodextrin; Leishmaniasis; Liposomes; Meglumine antimoniate; Pentavalent antimonials

Indexed keywords

ANTIMONY; ANTITRYPANOSOMAL AGENT; LIPOSOME; ORGANOMETALLIC COMPOUND;

ANIMAL; CHEMISTRY; DRUG EFFECT; HUMAN; LEISHMANIA; LEISHMANIASIS; REVIEW; SYNTHESIS;

ANIMALS; ANTIMONY; HUMANS; LEISHMANIA; LEISHMANIASIS; LIPOSOMES; ORGANOMETALLIC COMPOUNDS; TRYPANOCIDAL AGENTS;

EID: 68649102607     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules14072317     Document Type: Review

References (102)

1. Allan, J.W. Persian Metal Technology 700-1300 A.D.; Ithaca Press: London, UK, 1979; pp. 55- 59.
2. Savage-Smith, E. In Dioscorides on Pharmacy and Medicine; Riddle, J.M., Ed.; University of Texas Press: Austin, TX, USA, 1985; pp. 96-97.
3. Estes, J.W. The Medical Skills of Ancient Egypt; Science History Publications: Canton, MA, USA, 1989; p. 155.
4. Duffin, J.; René, P. "Anti-moine; Anti-biotique": The public fortunes of the secret properties of antimony potassium tartrate (tartar emetic). J. Hist. Med. Allied Sci. 1991, 46, 440-456.
5. World Health Organization. Leishmaniasis. http://apps.who.int/tdr/svc/ diseases/leishmaniasis/.
6. Vianna, G. Tratamento da leishmaniose tegumentar por injeçõ es intravenosas de tártaro emético. 7 Congresso Brasileiro de Medicina Tropical de São Paulo, São Paulo, Brasil, 1912, 4, 426-428.
7. Di Cristina, G.; Caronia, G. Sulla terapia della leishmaniosi interna. Pathologica 1915, 7, 82-83.
8. Cole, A.C.E. Kala-azar in east Africa. Trans. R. Soc. Trop. Med. Hyg. 1944, 37, 409-435.
9. Cook, C. Leonard Rogers KCSI FRCP FRS (1868-1962) and the founding of the Calcutta School of Tropical Medicine. Notes Rec. R. Soc. 2006, 60, 171-181.
10. Marsden, P.D. Pentavalent antimonials: old drugs for new diseases. Rev. Soc. Bras. Med. Trop. 1985, 18, 187-198.
11. Berman, J.D. Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in the last 10 years. Clin. Infect. Dis. 1997, 24, 684-703.
12. Guerin, P.J.; Olliaro, P.; Sundar, S.; Boelaert, M.; Croft, S.L.; Desjeux, P.; Wasunna, M.K.; Bryceson, A.D. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect. Dis. 2002, 2, 494-501. (Pubitemid 34826855)
13. Ridley, R.G. In Drug against parasitic diseases; Failamb, A.H., Ridley, R.G., Vial, H.J., Eds.; UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR): Geneva, Switzerland, 2003; pp. 13-21.
14. Murray, H.W. Progress in the treatment of a neglected infectious disease: Visceral leishmaniasis. Expert Rev. Anti Infect. Ther. 2004, 2, 279-292.
15. Meyerhoff, A. U.S. Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis. Clin. Infect. Dis. 1999, 28, 42-48.
16. Sundar, S.; Jha, T.K.; Thakur, C.P.; Engel. J.; Sindermann, H.; Fischer, C.; Junge, K.; Bryceson, A.; Berman, J. Oral Miltefosine for Indian Visceral Leishmaniasis. N. Engl. J. Med. 2002, 347, 1739-1746.
17. Steck, E.A. The leishmaniases. Prog. Drug Res. 1974, 18, 289-351.
18. Sundar, S.; Sinha, P.R.; Agrawal, N.K.; Srivastava, R.; Rainey, P.M.; Berman, J.D.; Murray, H.W.; Singh, V.P. A cluster of cases of severe cardiotoxicity among kala-azar patients treated with a high-osmolarity lot of sodium antimony gluconate. Am. J. Trop. Med. Hyg. 1998, 59, 139- 143.
19. Deps, P.D.; Viana, M.C.; Falqueto, A.; Dietze, R. Avaliação comparativa da eficácia e toxicidade do antimoniato de N-metil-glucamina e do Estibogluconato de Sódio BP88® no tratamento da leishmaniose cutânea localizada. Rev. Soc. Bras. Med. Trop. 2000, 33, 535-543.
20. Yan, S.; Jin, L.; Sun, H. The Use of Metals in Medicine. In Metallotherapeutic Drugs and Metal- Based Diagnostic Agents; Gielen, M., Tiekink, E.R.T., Eds.; John Wiley & Sons: New York, NY, USA, 2005; Vol. 10, pp. 441-461.
21. Headley, J.V.; Yong, M.S.; Brooks, P.W.; Phillips, A. Fast-Atom bombardment mass spectrometry of the organometallic parasiticide, meglumine antimonite. Rapid Comm. Mass Spectrom. 1995, 9, 372-376.
22. Roberts, W.L.; McMurray, W.J.; Rainey, P.M. Characterization of the antimonial antileishmanial agent meglumine antimonate (Glucantime). Antimicrob. Agents Chemother. 1998, 42, 1076-1082.
23. Frézard, F.; Martins, P.S.; Barbosa, M.C.M.; Pimenta, A.M.C.; Ferreira, W.A.; de Melo, J.E.; Mangrum, J.B.; Demicheli, C. New insights into the chemical structure and composition of the pentavalent antimonial drugs, meglumine antimonate and sodium stibogluconate. J. Inorg. Biochem. 2008, 102, 656-665.
24. Berman, J.D.; Grogl, M. Leishmania mexicana: chemistry and biochemistry of sodium stibogluconate (Pentostam). Exp. Parasitol. 1988, 67, 96-103.
25. Hansen, H.R.; Hansen, C.; Jensen, K.P.; Hansen, S.H.; Sturup, S.; Gammelgaard, B. Characterization of sodium stibogluconate by online liquid separation cell technology monitored by ICPMS and ESMS and computational chemistry. Anal. Chem. 2008, 80, 5993-6000.
26. Demicheli, C.; Ochoa, R.; Lula, I.S.; Gozzo, F.C.; Eberlin, M.; Frézard, F. Pentavalent organoantimonial derivatives: two simple and efficient synthetic methods for meglumine antimonate. Applied Organomet. Chem. 2003, 17, 226-231.
27. Goodwin, L.C.; Page, J.E. A study of the excretion of organic antimonials using a polarographic procedure. Biochem. J. 1943, 22, 236-240.
28. Burguera, J.L.; Burguera, M.; Petit de Pena, Y.; Lugo, A.; Anez, N. Selective determination of antimony(III) and antimony(V) in serum and urine and of total antimony in skin biopsies of patients with cutaneous leishmaniasis treated with meglumine antimoniate. Trace Elem. Med. 1993, 10, 66-70.
29. Shaked-Mishan, P.; Ulrich, N.; Ephros, M.; Zilberstein, D. Novel intracellular Sb(V) reducing activity correlates with antimony susceptibility in Leishmania donovani. J. Biol. Chem. 2001, 276, 3971-3976.
30. Ferreira, C.S.; Martins, P.S.; Demicheli, C.; Brochu, C.; Ouellette,M.; Frézard, F. Thiol-induced reduction of antimony(V) into antimony(III): a comparative study with trypanothione, cysteinylglycine, cysteine and glutathione. BioMetals 2003, 16, 441-443.
31. Frézard, F.; Demicheli, C.; Ferreira, C.S.; Costa, M.A.P. Glutathione-induced conversion of pentavalent antimony to trivalent antimony in meglumine antimoniate. Antimicrob. Agents Chemother. 2001, 45, 913-916.
32. Yan, S.C.; Li, F.; Ding, K.Y.; Sun, H. Reduction of pentavalent antimony by trypanothione and formation of a binary and ternary complex of antimony(III) and trypanothione. J. Biol. Inorg. Chem. 2003, 8, 689-697.
33. Mego, J.L. Stimulation of intralysosomal proteolysis by cysteinyl-glycine, a product of the action of gamma-glutamyl transpeptidase on glutathione. Biochim. Biophys. Acta 1985, 841, 139-144.
34. Gainey, D.; Short, S.; McCoy, K.L. Intracellular location of cysteine transport activity correlates with productive processing of antigen disulfide. J. Cell Physiol. 1996, 168, 248-254.
35. Fairlamb, A.H.; Cerami, A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu. Rev. Microbiol. 1992, 46, 695-729.
36. Denton, H.; McGregor, J.C.; Coombs, G.H. Reduction of anti-leishmanial pentavalent antimonial drugs by a parasite-specific thiol-dependent reductase, TDR1. Biochem. J. 2004, 381, 405-412.
37. Zhou, Y.; Messier, N.; Ouellette, M.; Rosen, B.P.; Mukhopadhyay, R. Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug Pentostam. J. Biol. Chem. 2004, 279, 37445-37451.
38. Gourbal, B.; Sonuc, N.; Bhattacharjee, H.; Legare, D.; Sundar, S.; Ouellette, M.; Rosen, B.P.; Mukhopadhyay, R. Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J. Biol. Chem. 2004, 279, 31010-31017. (Pubitemid 39037760)
39. Sun, H.; Yan, S.C.; Cheng, W.S. Interaction of antimony tartrate with the tripeptide glutathione. Eur. J. Biochem. 2000, 267, 5450-5457.
40. Mukhopadhyay, R.; Dey, S.; Xu, N.; Gage, D.; Lightbody, J.; Ouellette, M.; Rosen, B.P. Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania. Proc. Natl. Acad. Sci. USA 1996, 93, 10383-10387.
41. Légaré, D.; Richard, D.; Mukhopadhyay, R.; Stierhof, Y.D.; Rosen, B.P.; Haimeur, A.; Papadopoulou, B.; Ouellette, M. The Leishmania ATP-binding cassette protein PGPA is an intracellular metalthiol transporter ATPase. J. Biol. Chem. 2001, 276, 26301-26307.
42. Ouellette, M.; Drummelsmith, J.; Papadopoulou, B. Leishmaniasis: drugs in the clinic, resistance and new developments. Drug Resist. Updat. 2004, 7, 257-266.
43. Carter, K.C.; Sundar, S.; Spickett, C.; Pereira, O.C.; Mullen, A.B. The in vivo susceptibility of Leishmania donovani to sodium stibogluconate is drug specific and can be reversed by inhibiting glutathione biosynthesis. Antimicrob. Agents Chemother. 2003, 47, 1529-1535.
44. Krauth-Siegel, R.L.; Comini, M.A. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim. Biophys. Acta 2008, 1780, 1236-1248.
45. Cunningham, M.L.; Fairlamb, A.H. Trypanothione reductase from Leishmania donovani. Purification, characterisation and inhibition by trivalent antimonials. Eur. J. Biochem. 1995, 230, 460-468.
46. Wyllie, S.; Cunningham, M.L.; Fairlamb, A.H. Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani. J. Biol. Chem. 2004, 279, 39925-39993.
47. Baiocco, P.; Colotti, G.; Franceschini, S.; Ilari, A. Molecular basis of antimony treatment in leishmaniasis. J. Med. Chem. 2009, 52, 2603-2612.
48. Demicheli, C.; Frézard, F.; Mangrum, J.B.; Farrell, N.P. Interaction of trivalent antimony with a CCHC zinc finger domain: potential relevance to the mechanism of action of antimonial drugs. Chem. Commun. 2008; 39, 4828-4830.
49. Leon, O.; Roth, M. Zinc fingers: DNA binding and protein-protein interactions. Biol. Res. 2000, 33, 21-30.
50. Webb, J.R.; McMaster, W.R. Molecular cloning and expression of a Leishmania major gene encoding a single-stranded DNA-binding protein containing nine "CCHC" zinc finger motifs. J. Biol. Chem. 1993, 268, 13994-14002.
51. Sereno, D.; Holzmuller, P.; Mangot, I.; Cuny, G.; Ouaissi, A.; Lemesre, J. Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes Antimicrob. Agents Chemother. 2001, 45, 2064-2069. (Pubitemid 32591699)
52. Sudhandiran, G.; Shaha, C. Antimonial induced increase in intracellular Ca2+ through nonselective cation channels in the host and the parasite is responsible for apoptosis of intracellular Leishmania donovani amastigotes. J. Biol. Chem. 2003, 278, 25120-25132.
53. Mukherjee, S.B.; Das, M.; Sudhandiran, G.; Shaha, C. Increase in cytosolic Ca2+ levels through the activation of non-selective cation channels induced by oxidative stress causes mitochondrial depolarization leading to apoptosis-like death in Leishmania donovani promastigotes. J. Biol. Chem. 2002, 277, 24717-24727.
54. Chakraborty, A.K.; Majumder, H.K. Mode of action of pentavalent antimonials: specific inhibition of type I DNA topoisomerase of Leishmania donovani. Biochem. Biophys. Res. Commun. 1988, 152, 605-611.
55. Walker, J.; Saravia, N.G. Inhibition of Leishmania donovani promastigote DNA topoisomerase I and human monocyte DNA topoisomerases I and II by antimonial drugs and classical antitopoisomerase agents. J. Parasitol. 2004, 90, 1155-1162.
56. Lucumi, A.; Robledo, S.; Gama, V.; Saravia, N.G. Sensitivity of Leishmania Viannia panamensis to pentavalent antimony is correlated with the formation of cleavable DNA-protein complexes. Antimicrob. Agents Chemother. 1998, 42, 1990-1995.
57. Demicheli, C.; Frézard, F.; Lecouvey, M.; Garnier-Suillerot, A. Antimony(V) complex formation with adenine nucleosides in aqueous solution. Biochim. Biophys. Acta 2002, 1570, 192-198.
58. Chai, Y.; Yan, S.; Wong, I.L.K.; Chow, L.M.C.; Sun, H. Complexation of antimony [Sb(V)] with guanosine 5'-monophosphate and guanosine 5'-diphospho-D-mannose: formation of both monoand bis-adducts. J. Inorg. Biochem. 2005, 99, 2257-2263.
59. Demicheli, C.; Santos, L.S.; Ferreira, C.S.; Bouchemal, N.; Hantz, E.; Eberlin, M.N.; Frézard, F. Synthesis and characterization of Sb(V)-adenosine and Sb(V)-guanosine complexes in aqueous solution. Inorganica Chim. Acta 2006, 359, 159-167.
60. Ferreira, C.S.; Pimenta, A.M.C.; Demicheli, C.; Frézard, F. Characterization of reactions of antimoniate and meglumine antimoniate with a guanine ribonucleoside at different pH. Biometals 2006, 19, 573-581.
61. Hansen, H.R.; Pergantis, S.A. Mass spectrometric identification and characterization of antimony complexes with ribose-containing biomolecules and an RNA oligomer. Anal. Bioanal. Chem. 2006, 385, 821-833.
62. Roberts, W.L.; Berman, J.D.; Rainey, P.M. In vitro antileishmanial properties of tri- and pentavalent antimonial preparations. Antimicrob. Agents Chemother. 1995, 39, 1234-1239.
63. Marr, J. Purine analogs as chemotherapeutic agents in leishmaniasis and American trypanosomiasis. J. Lab. Clin. Med. 1991, 118, 111-119.
64. Berman, J.D.; Waddell, D.; Hanson, B.D. Biochemical mechanisms of the antileishmanial activity of sodium stibogluconate. Antimicrob. Agents Chemother. 1985, 27, 916-920.
65. Berman, J.D.; Gallalee, J.V.; Best, J.M. Sodium stibogluconate (Pentostam) inhibition of glucose catabolism via the glycolytic pathway, and fatty acid beta-oxidation in Leishmania mexicana amastigotes. Biochem. Pharmacol. 1987, 36, 197-201.
66. Murray, H.W. Clinical and experimental advances in treatment of visceral leishmaniasis. Antimicrob. Agents Chemother. 2001, 45, 2185-2197.
67. Pathak, M.K.; Yi, T. Sodium stibogluconate is a potent inhibitor of protein tyrosine phosphatases and augments cytokine responses in hemopoietic cell lines. J. Immunol. 2001, 167, 3391-3397.
68. Muniz-Junqueira, M.I.; Paula-Coelho, V.N. Meglumine antimonate directly increases phagocytosis, superoxide anion and TNF-? production, but only via TNF-? it indirectly increases nitric oxide production by phagocytes of healthy individuals, in vitro. Int. Immunopharmacol. 2008, 8, 1633-1638.
69. Murray, H.W.; Berman, J.D.; Wright, S.D. Immunochemotherapy for intracellular Leishmania donovani infection: gamma interferon plus pentavalent antimony. J. Infect. Dis. 1988, 157, 973-978.
70. Machado-Pinto, J.; Pinto, J.; Da Costa, C.A.; Genaro, O.; Marques, M.J.; Modabber, F.; Mayrink, W. Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed Leishmania (Leishmania) amazonensis vaccine plus antimonial. Int. J. Dermatol. 2002, 41, 73-78.
71. Gailliot, P.L. Procédé de préparation de dérivés de l'antimoine. (Societé des usines chimiques de Rhone-Poulenc). FR Patent 8.687.47, 1941.
72. Joan, F.B.; Concepcio, M.C. New procedure for the preparation of antimonic acid derivatives applicable in the treatment of canine leishmaniosis. ES Patent 2.050.614, 1994.
73. Demicheli, C. Síntese de derivados de antimônio pentavalente utilizados no tratamento de protozoonoses. Brazil Patent Pending PI 9907575-0, 1999.
74. Demicheli, C.; Frézard, F. Novo processo para preparaç ão de derivados de antimônio. Brazil Patent Pending PI 0106305-7, 2001.
75. De Morais-Teixeira, E.; De Carvalho, A.S.; Da Costa, J.C.S.; Duarte, S.L.; Mendonça, J.S.; Boechat, N.; Rabello, A. In vitro and in vivo activity of meglumine antimoniate produced at Farmanguinhos-Fiocruz, Brazil, against Leishmania (Leishmania) amazonensis, L (L.) chagasi and L (Viannia) braziliensis. Mem. Inst. Oswaldo Cruz 2008, 10, 358-362.
76. Dzamitika, S.A.; Falcão, C.A.; Oliveira, F.B.; Marbeuf, C.; Garnier-Suillerot, A.; Demicheli, C.; Rossi-Bergmann, B.; Frézard, F. Role of residual Sb(III) in meglumine antimoniate cytotoxicity and MRP1-mediated resistance. Chem. Biol. Int. 2006, 160, 217-224.
77. Bangham, A.D.; Standish, M.M.; Watkins, J.C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol. 1965, 13, 238-252.
78. Alving, C.R.; Steck, E.A.; Chapman, W.L.; Waits, V.B.; Hendricks, L.D.; Swartz, G.M.; Hanson, W.L. Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs. Proc. Natl. Acad. Sci. USA 1978, 75, 2959-2963.
79. New, R.R.; Chance, M.L.; Thomas, S.C.; Peters, W. Antileishmanial activity of antimonials entrapped in liposomes. Nature 1978, 272, 55-56.
80. Chapman, W.L.; Hanson, W.L.; Alving, C.R.; Hendricks, L.D. Antileishmanial activity of liposome-encapsulated meglumine antimonate in the dog. Am. J. Vet. Res. 1984, 45, 1028-1030.
81. Collins, M.; Carter, K.C.; Baillie, A.J.; O'Grady, J. The distribution of free and non-ionic vesicular sodium stibogluconate in the dog. J. Drug Target. 1993, 1, 133-142.
82. Alving, C.R.; Swartz, G.M. In Liposome technology; Gregoriadis, G., Ed.; CRC Press: Boca Raton, FL, USA, 1984; Vol. 2, pp. 55-68.
83. Rao, L.S. Anti-leishmanial pharmaceutical formulation. US Patent 4.594.241, 1986.
84. Schettini, D.A.; Ribeiro, R.R.; Demicheli, C.; Rocha, O.G.F.; Melo, M.N.; Michalick, M.S.M.; Frézard, F. Improved targeting of antimony to the bone marrow of dogs using liposomes of reduced size. Int. J. Pharm. 2006, 315,140-147.
85. Frézard, F.; Michalick, M.S.M.; Soares, C.F.; Demicheli, C. Novel methods for the encapsulation of meglumine antimoniate in liposomes. Braz. J. Med. Biol. Res. 2000, 33, 841-846.
86. Frézard, F.; Demicheli, C.; Schettini, D.A.; Ribeiro, R.R.; Melo, M.N.; Michalick, M.S.M. Processo para a preparação de formulações farmacêuticas do antimoniato de meglumina em lipossomas e uso das formulações farmacêuticas em animais acometidos com leishmaniose visceral. Brazil Patent Pending PI0405489-0, 2004.
87. Demicheli, C.; Rocha, O.G.F.; Schettini, D.A.; Frézard, F. Liposomes: physicochemical and pharmacological properties, applications in antimony-based chemotherapy. Quim. Nova 2005, 28, 511-518.
88. Oliva, G.; Gradoni, L.; Ciaramella, P.; De Luna, R.; Cortese, L.; Orsini, S.; Davidson, R.N.; Persechino, A. Activity of liposomal amphotericin B (AmBisome) in dogs naturally infected with Leishmania infantum. J. Antimicrob. Chemother. 1995, 36, 1013-1019.
89. Valladares, J.E.; Freixas, J.; Alberola, J.; Franquelo, C.; Cristofol, C.; Arboix, M. Pharmacokinetics of liposome-encapsulated meglumine antimoniate after intramuscular and subcutaneous administration in dogs. Am. J. Med. Hyg. 1997, 57, 403-406.
90. Valladares, J.E.; Riera, C.; González-Ensenyat, P.; Díez-Cascón, A.; Ramos, G.; Solano-Gallego, L.; Gállego, M.; Gállego, M.; Portús, N.; Arboix, M.; Alberola, J. Long term improvement in the treatment of canine leishmaniosis using antimony liposomal formulation. Vet. Parasitol. 2001, 97, 15-21.
91. Nieto, J.; Alvar, J.; Mullen, K.C.; Carter, K.C.; Rodríguez, C.; San Andrés, M.I.; San Andrés, M.D.; Baillie, A.J.; Gonzalez, F. Pharmacokinetics, toxicities, and efficacies of sodium stibogluconate formulations after intravenous administration in animals. Antimicrob. Agents Chemother. 2003, 47, 2781-2787.
92. Schettini, D.A.; Costa Val, A.P.; Souza, L.F.; Demicheli, C.; Rocha, O.G.F.; Melo, M.N.; Michalick, M.S.M.; Frézard, F. Distribution of liposome-encapsulated antimony in dogs. Braz. J. Med. Biol. Res. 2003, 36, 269-272.
93. Schettini, D.A., Costa Val, A.P.; Souza, L.F.; Demicheli, C.; Rocha, O.G.F.; Melo, M.N.; Michalick, M.S.M.; Frézard, F. Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with visceral leishmaniasis submitted to multiple dose treatment with liposomeencapsulated meglumine antimoniate. Braz. J. Med. Biol. Res. 2005, 38, 1879-1883.
94. Ribeiro, R.R.; Moura, E.P.; Pimentel, V.M.; Sampaio, W.M.; Silva, S.M.; Schettini, D.A.; Alves, C.F.; Melo, F.A.; Tafuri, W.L.; Demicheli, C.; Melo, M.N.; Frezard, F.; Michalick, M.S.M. Reduced tissue parasitic load and infectivity to sand flies in dogs naturally infected by Leishmania (Leishmania) chagasi following treatment with a liposome formulation of meglumine antimoniate. Antimicrob. Agents Chemother. 2008, 52, 2564-2572.
95. Costa-val, A.P. Tratamento da leishmaniose visceral canina com antimonial pentavalente encapsulado em lipossomas. Thesis, Universidade Federal de Minas Gerais: Belo Horizonte, Brazil, 2004; p.125.
96. Szebeni, J. The interaction of liposomes with the complement system. Crit. Rev. Ther. Drug Carrier Syst. 1998, 15, 57-58.
97. Irie, T.; Uekama, K. Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation. J. Pharm. Sci. 1997, 86, 147-162.
98. Hirayama, F.; Uekama, K. Cyclodextrin-based controlled drug release system. Adv. Drug Deliv. Rev. 1999, 36, 125-141.
99. Demicheli, C.; Frézard, F.J.G.; Millán, R.D.S.; Bejarano, R.O.; Ferreira, L.A.M.; da Silva, J.B.B.; de Melo, A.L. Processo de Preparação de Compostos entre as ciclodextrinas ou seus derivados e o antimônio ou seus derivados, de formulações farmacêuticas contendo esses compostos e produtos associados, para tratamento das leishmanioses e da esquitossomose. Brazil Patent Pending PI0304952-3, 2003.
100. Demicheli, C.; Ochoa, R.; Silva, J.B.B.; de Melo, A.L.; Falcão, C.A.M.; Rossi-Bergmann, B.; Sinisterra, R.D.; Frézard, F. Oral delivery of meglumine antimoniate-beta-cyclodextrin complex for treatment of leishmaniasis. Antimicrob. Agents Chemother. 2004, 48, 100-103.
101. Martins, P.S.; Ochoa, R.; Pimenta, A.M.C.; Ferreira, L.A.M.; de Melo, A.L.; da Silva, J.B.B.; Sinisterra, R.D.; Demicheli, C.; Frézard, F. Mode of action of β-cyclodextrin as an absorption enhancer of the water-soluble drug meglumine antimoniate. Int. J. Pharm. 2006, 325, 39-47.
102. Frézard, F.; Martins, P.S.; Bahia, A.P.C.O.; Le Moyec, L.; de Melo, A.L.; Pimenta, A.M.C.; Salerno, M.; da Silva, J.B.B.; Demicheli, C. Enhanced oral delivery of antimony from meglumine antimoniate/β- cyclodextrin nanoassemblies. Int. J. Pharm. 2008, 347, 102-108.