期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 64, 期 7, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00234-20
关键词
PEG; allopurinol; antimony; dogs; drug delivery; drug resistance; liposomes; meglumine antimoniate; visceral leishmaniasis
资金
- Brazilian agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [305659/2017-0, 402634/2013-6]
- Brazilian agency Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) [APQ-03129-16]
- Brazilian agency Pro-Reitoria de Pesquisa da UFMG (PRPq/UFMG)
- Brazilian agency Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- CNPq
The treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote a marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP plus Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg of body weight/dose) at 4-day intervals plus allopurinol at 30 mg/kg/12 h per os (p.o.) during 130 days (LCP+Allop); LC plus Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) plus allopurinol during 130 days (LC+Allop); Allop, treated with allopurinol only; and a nontreated control. Parasite loads were evaluated by quantitative PCR in liver, spleen, and bone marrow tissue and by immunohistochemistry in the ear skin, before treatment, just after treatment, and 4 months later. The LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen, and bone marrow 4 months after treatment compared to the pretreatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin in comparison to the control group. On the basis of clinical staging and parasitological evaluations, the LCP formulation exhibited a more favorable therapeutic profile than the LC one, being therefore promising for the treatment of canine visceral leishmaniasis.
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