title: Oral delivery of meglumine antimoniate-beta-cyclodextrin complex for treatment of leishmaniasis.
abstract: The need for daily parenteral administration represents one of the most serious limitations in the clinical use of pentavalent antimonials against leishmaniasis. In this work, we investigated the ability of beta-cyclodextrin to enhance the oral absorption of antimony and to promote the oral efficacy of meglumine antimoniate against experimental cutaneous leishmaniasis. The occurrence of interactions between beta-cyclodextrin and meglumine antimoniate was demonstrated through the changes induced in the spin lattice relaxation times of protons in both compounds. When free and complexed meglumine antimoniate were given orally to Swiss mice, plasma antimony levels were found to be about three times higher for the meglumine antimoniate-beta-cyclodextrin complex than for the free drug. Antileishmanial efficacy was evaluated in BALB/c mice experimentally infected with Leishmania amazonensis. Animals treated daily with the complex (32 mg of Sb/kg of body weight) by the oral route developed significantly smaller lesions than those treated with meglumine antimoniate (120 mg of Sb/kg) and control animals (treated with saline). The effectiveness of the complex given orally was equivalent to that of meglumine antimoniate given intraperitoneally at a twofold-higher antimony dose. The antileishmanial efficacy of the complex was confirmed by the significantly lower parasite load in the lesions of treated animals than in saline-treated controls. This work reports for the first time the effectiveness of an oral formulation for pentavalent antimonials.
authors.affiliation: Departamento de Química, ICEX, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Demicheli
authors.forename: Rosemary
authors.initials: R
authors.lastname: Ochoa
authors.forename: José B B
authors.initials: JB
authors.lastname: da Silva
authors.forename: Camila A B
authors.initials: CA
authors.lastname: Falcão
authors.forename: Bartira
authors.initials: B
authors.lastname: Rossi-Bergmann
authors.forename: Alan L
authors.initials: AL
authors.lastname: de Melo
authors.forename: Ruben D
authors.initials: RD
authors.lastname: Sinisterra
authors.forename: Frédéric
authors.initials: F
authors.lastname: Frézard
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007408:Intestinal Absorption; D007894:Leishmania mexicana; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008536:Meglumine / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use*; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use*; D047392:beta-Cyclodextrins
chemical_list: D000981:Antiprotozoal Agents; D003505:Cyclodextrins; D009942:Organometallic Compounds; D047392:beta-Cyclodextrins; D008536:Meglumine; D000077485:Meglumine Antimoniate; C031215:betadex