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There are a limited number of chemotherapeutic agents for the treatment canine visceral leishmaniasis (CVL). This study aimed to formulate and assess micellar formulation of miltefosine (MTF) to increase antileishmanial therapeutic effects in dogs naturally infected by Leishmania (L) infantum for the first time. MTF loaded pluronic F127 (PF/MTF) micelles were formulated and coated with chitosan (Cs/PF/MTF). Toxicity of compounds was evaluated. The in vitro and in vivo antileishmanial effect of Cs/PF/MTF was examined in L. infantum promastigotes and amastigotes as well as naturally infected dogs by L. infantum. In-vitro efficacy studies in promastigotes and amastigotes demonstrated that inhibitory concentration (IC50) of Cs/PF/MTF was significantly lower in comparison to miltefosine. In vivo data showed that Cs/PF/MTF is more effective against CVL compared with miltefosine alone. The result of this study indicated that intravenous injection of new formulation of Cs/PF/MTF was tolerated and treated on L. infantum naturally infected dogs with the dosages of 170 μg/kg daily for 28 days., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study was designed to evaluate the safety, immunogenicity, and efficacy of a single dose of L. infantum (LiCen -/- ) live attenuated candidate vaccine against canine leishmaniasis (CanL). Eighteen healthy domestic dogs with no anti-Leishmania antibodies and negative leishmanin skin test (LST) were randomly inoculated intravenously with either L. infantum (LiCen -/- ) vaccine candidate in 10 dogs or phosphate-buffered saline (PBS) in 8 dogs. The safety, immunogenicity, and efficacy rate of L. infantum (LiCen -/- ) vaccine candidate against CanL were evaluated by different criteria, including clinical manifestations, injection-site lesion, hematology and biochemistry values, anti-Leishmania antibodies using direct agglutination test (DAT), delayed-type hypersensitivity (DTH) using LST, and CD4 + and CD8 + T-cells subsets, as well as by measuring interferon (IFN-γ), interleukin (IL-23), IL-17, and IL-10 cytokines. Spleen aspiration and detection of Leishmania parasite using parasitological examinations (microscopy and culture) were performed in both vaccinated and control groups. Two months after intervention, each dog was challenged intraperitoneally (IP) with wide type (WT) L. infantum. Two-month follow-up post vaccination showed no clinical signs and serious side effects associated with the vaccination. A significant increase was found in the expression of IL-17, CD4 + , and CD8 + gene transcripts in PBMCs, as well as increased levels of Th1 cytokines, and reduction of Th2 cytokine. The efficacy of the vaccine candidate was calculated to be 42.85%. While the time window for assessing the vaccine's effectiveness was too limited to draw any real conclusions but the preliminary results showed a moderate efficacy rate due to inoculation a single dose of L. infantum (LiCen -/- ) vaccine candidate. Further investigations with more sample sizes and multiple doses of the vaccine candidate using natural challenges in the endemic areas of CanL are recommended., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or persona,relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)