Therapeutic Efficacy of a Mixed Formulation of Conventional and PEGylated Liposomes Containing Meglumine Antimoniate, Combined with Allopurinol, in Dogs Naturally Infected with Leishmania infantum.

Autor:	Dos Santos CCP; Departamento de Fisiologia e Biofísica-ICB, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Ramos GS; Departamento de Fisiologia e Biofísica-ICB, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., De Paula RC; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia (UFU), Uberlândia, Minas Gerais, Brazil., Faria KF; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia (UFU), Uberlândia, Minas Gerais, Brazil., Moreira POL; Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz Minas, Belo Horizonte, Minas Gerais, Brazil., Pereira RA; Departamento de Patologia-ICB, UFMG, Belo Horizonte, Minas Gerais, Brazil., Melo MN; Departamento de Parasitologia-ICB, UFMG, Belo Horizonte, Minas Gerais, Brazil., Tafuri WL; Departamento de Patologia-ICB, UFMG, Belo Horizonte, Minas Gerais, Brazil., Demicheli C; Departamento de Química-ICEX, UFMG, Belo Horizonte, Minas Gerais, Brazil., Ribeiro RR; Departamento de Medicina Veterinária, Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, Minas Gerais, Brazil., Azevedo EG; Departamento de Farmácia, UFJF, Governador Valadares, Minas Gerais, Brazil., Do Monte-Neto R; Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz Minas, Belo Horizonte, Minas Gerais, Brazil., Da Silva SM; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia (UFU), Uberlândia, Minas Gerais, Brazil., Frézard F; Departamento de Fisiologia e Biofísica-ICB, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil frezard@icb.ufmg.br.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2020 Jun 23; Vol. 64 (7). Date of Electronic Publication: 2020 Jun 23 (Print Publication: 2020).
DOI:	10.1128/AAC.00234-20
Abstrakt:	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. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
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