Distribution of liposome-encapsulated antimony in dogs

Schettini, Dante A.; Val, Adriane P. Costa; Souza, Lucas Fernandes; Demicheli, Cynthia; Rocha, Olguita Geralda Ferreira; Melo, Maria Norma; Michalick, Marilene Suzan Marques; Frézard, Frédéric

doi:10.1590/s0100-879x2003000200015

Cited by 15 publications

(8 citation statements)

References 11 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, we have reported the distribution of antimony (Sb) in healthy dogs, following a single intravenous (iv) bolus injection of LMA. The latter study suggested that the critical organ for the treatment with LMA could be the bone marrow, since it showed very low antimony levels (5), and that a multiple dose regimen would be required to achieve therapeutic levels of antimony in this tissue. On the other hand, the impact of infection on the capture of liposomes by this tissue has not yet been documented.…”

Section: Da Schettini Et Almentioning

confidence: 99%

“…Meglumine antimoniate was encapsulated in freeze-dried liposomes as previously described (4,5). Briefly, small unilamellar vesicles were prepared in water from L-α-distearoylphosphatidylcholine, cholesterol and dicetylphosphate (molar ratio of 5:4:1) at a final lipid concentration of 55 g/L.…”

Section: Da Schettini Et Almentioning

confidence: 99%

“…The antimony levels in the bone marrow of dogs following treatment with free and liposome-encapsulated antimonials have been reported in two previous studies (5,8). However, these studies used healthy animals and did not evaluate the effect of multiple dose treatment.…”

Section: Da Schettini Et Almentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with visceral leishmaniasis submitted to multiple dose treatment with liposome-encapsulated meglumine antimoniate

Schettini

Val

Souza

et al. 2005

Braz J Med Biol Res

Self Cite

View full text Add to dashboard Cite

The aim of the present study was to evaluate the impact of a multiple dose regimen of a liposomal formulation of meglumine antimoniate (LMA) on the pharmacokinetics of antimony in the bone marrow of dogs with visceral leishmaniasis and on the ability of LMA to eliminate parasites from this tissue. Dogs naturally infected with Leishmania chagasi received 4 intravenous doses of either LMA (6.5 mg antimony/kg body weight, N = 9), or empty liposomes (at the same lipid dose as LMA, N = 9) at 4-day intervals. A third group of animals was untreated (N = 8). Before each administration and at different times after treatment, bone marrow was obtained and analyzed for antimony level (LMA group) by electrothermal atomic absorption spectrometry, and for the presence of Leishmania parasites (all groups). There was a significant increase of antimony concentration from 0.76 µg/kg wet organ (4 days after the first dose) to 2.07 µg/kg (4 days after the fourth dose) and a half-life of 4 days for antimony elimination from the bone marrow. Treatment with LMA significantly reduced the number of dogs positive for parasites (with at least one amastigote per 1000 host cells) compared to controls (positive dogs 30 days after treatment: 0 of 9 in the LMA group, 3 of 9 in the group treated with empty liposomes and 3 of 8 in the untreated group). However, complete elimination of parasites was not achieved. In conclusion, the present study showed that multiple dose treatment with LMA was effective in improving antimony levels in the bone marrow of dogs with visceral leishmaniasis and in reducing the number of positive animals, even though it was not sufficient to achieve complete elimination of parasites.

show abstract

Section: Da Schettini Et Almentioning

confidence: 99%

Section: Da Schettini Et Almentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with visceral leishmaniasis submitted to multiple dose treatment with liposome-encapsulated meglumine antimoniate

Schettini

Val

Souza

et al. 2005

Braz J Med Biol Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…Estudos de biodistribuição/farmacocinética do antimônio em camundongos e cães mostraram que a forma lipossomal promove níveis de antimônio muito mais elevados e prolongados no fígado e no baço dos animais quando comparado à forma livre 21,22 . Essa diferença de biodistribuição entre as formas livre e encapsulada é ilustrada, na Tabela 2, a partir de dados obtidos em cães.…”

Section: Figura 4 Destino Dos Lipossomas Convencionais Por Via Endovunclassified

“…Vale ressaltar que o tamanho dos lipossomas é um parâmetro importante, pois tem influência tanto na taxa de eliminação do parasita 23 , quanto na concentração de antimônio ao nível da medula ós-sea 22 . Portanto, lipossomas pequenos (diâmetro < 200 nm) parecem ter acesso facilitado à medula óssea, o que é de interesse pois devem possibilitar a eliminação do parasita que se encontra nesse tecido.…”

Section: Figura 4 Destino Dos Lipossomas Convencionais Por Via Endovunclassified

Lipossomas: propriedades físico-químicas e farmacológicas, aplicações na quimioterapia à base de antimônio

Frézard¹,

Schettini²,

Rocha³

et al. 2005

Quím. Nova

View full text Add to dashboard Cite

Recebido em 24/5/04; aceito em 14/9/04; publicado na web em 17/2/05 LIPOSOMES: PHYSICOCHEMICAL AND PHARMACOLOGICAL PROPERTIES, APPLICATIONS IN ANTIMONY-BASED CHEMOTHERAPY. The use of organoantimonial complexes in the therapeutic of leishmaniasis and schistosomiasis has been limited mainly by the need for daily parenteral administration, their adverse side-effects and the appearance of drug resistance. Liposome encapsulation has been so far the most effective means to improve the efficacy of pentavalent antimonials against visceral leishmaniasis. Pharmacologically-and pharmaceutically-acceptable liposomal compositions are still being investigated through manipulation of preparation method, lipid composition and vesicle size. Recently, the encapsulation of a trivalent antimonial within "stealth" liposomes was found to reduce its acute toxicity and effectively deliver this compound to the parasite in experimental schistosomiasis.Keywords: liposomes; antimony; chemotherapy. INTRODUÇÃONo início do século passado, Gaspar Vianna, pesquisador pioneiro em doença de Chagas e leishmaniose, relatou a eficácia do complexo de antimônio trivalente (Sb(III)), tártaro emético, no tratamento da leishmaniose muco-cutânea 1 . Da mesma forma, o tártaro emético foi o primeiro medicamento empregado com êxito no tratamento da esquistossomose 2,3 . Entretanto, o uso clínico deste composto foi interrompido, por causa de seus severos efeitos colaterais e da descoberta de novos fármacos menos tóxicos.A partir da década de 1940, complexos de antimônio pentavalente (Sb(V)) começaram a ser utilizados na terapêutica das leishmanioses 4 . Os principais antimoniais atualmente em uso são complexos de Sb(V) com o N-metil-glucamina (antimoniato de meglumina) e com o gluconato de sódio (estibogluconato de sódio). Até hoje, nem a estrutura desses compostos, nem seu mecanismo de ação foram completamente elucidados. Foi sugerido que o Sb(V) seria uma pró-droga, sendo reduzido no organismo hospedeiro a Sb(III) que seria a forma ativa e tóxica 5 . Recentemente, foi mostrado que os tióis podem estar envolvidos nesse processo de redução 6 . Embora os antimoniais pentavalentes continuem sendo os medicamentos de primeira escolha no tratamento de todas as formas de leishmanioses, o seu uso clínico apresenta várias limitações. Esses compostos devem ser administrados por via parenteral (injeção intravenosa ou intramuscular), diariamente, num período de 20-40 dias. Nesse contexto, efeitos colaterais são freqüentes Essencialmente duas estratégias diferentes estão atualmente disponíveis para o desenvolvimento de novos medicamentos. Uma estratégia envolve o planejamento/síntese de novas substâncias ativas ou de fármacos já conhecidos com modificações químicas; a outra envolve a associação reversível de fármacos já em uso a um sistema transportador, visando direcionar o fármaco para a célula alvo e evitar os locais indesejáveis onde o fármaco exerce toxicidade. Esta última estratégia, além de prolongar a validade de proteção por patente no uso do fármaco, oferece um...

show abstract

Drug Targets, Drug Effectors, and Drug Targeting and Delivery

Loiseau

Barratt

2012

Drug Resistance in Leishmania Parasites

View full text Add to dashboard Cite

Distribution of liposome-encapsulated antimony in dogs

Cited by 15 publications

References 11 publications

Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with visceral leishmaniasis submitted to multiple dose treatment with liposome-encapsulated meglumine antimoniate

Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with visceral leishmaniasis submitted to multiple dose treatment with liposome-encapsulated meglumine antimoniate

Lipossomas: propriedades físico-químicas e farmacológicas, aplicações na quimioterapia à base de antimônio

Drug Targets, Drug Effectors, and Drug Targeting and Delivery

Contact Info

Product

Resources

About