betadex and Leishmaniasis--Cutaneous

Euthanasia of animals is not accepted as a control for cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis and drugs used in humans for the treatment of leishmaniasis are not allowed for animals in Brazil. Miltefosine was authorized for dogs infected by Leishmania infantum with variable results for L. braziliensis. Thus, nine dogs infected with Leishmania (V.) braziliensis were treated by a combination of furazolidone and β-cyclodextrin. The nine dogs were mongrels, weighing between 4-17 kg and 3-10 years old. These dogs had ulcerous lesions in different regions such as scrotal tissue, auricular pavilion and nostrils. Serological, molecular and protozoal culture techniques were used for laboratory diagnosis. The treatment used furazolidone + β-cyclodextrin complex (1: 2) at a concentration of 60 mg/mL given orally at a dose of 15 mg/kg every 12 hours. The re-epithelialization of lesions occurred between 35 and 41 days of treatment. During fourteen months the animals were monitored and there was no reactivation of lesions or growth of the protozoan in a culture medium of the biopsies. This study demonstrated that treatment with FZD and CD is effective in reducing the cutaneous lesions caused by L. braziliensis in dogs.

Topics: Animals; Anti-Infective Agents, Local; beta-Cyclodextrins; Brazil; Dog Diseases; Dogs; Furazolidone; Humans; Leishmania braziliensis; Leishmaniasis, Cutaneous

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.

Topics: Administration, Oral; Animals; Antiprotozoal Agents; beta-Cyclodextrins; Chemical Phenomena; Chemistry, Physical; Cyclodextrins; Injections, Intraperitoneal; Intestinal Absorption; Leishmania mexicana; Leishmaniasis, Cutaneous; Male; Meglumine; Meglumine Antimoniate; Mice; Mice, Inbred BALB C; Organometallic Compounds