Camila S Freitas, Daniela P Lage, Breno L Pimenta, Saulo S G Dias, Karolina O M Falcão, Isabela A G Pereira, Ana L Silva, Luciana M R Antinarelli, Raquel S B Câmara, Marcelo M Jesus, Maíza M Rodrigues, Dóris M Abrão, Grasiele S V Tavares, Miguel A Chávez-Fumagalli, Bruno A Oliveira, Myron Christodoulides, Adilson D Silva, Elaine S Coimbra, Eduardo A F Coelho
{"title":"负载1,2,3-三唑衍生物的聚合物胶束:一种有希望的对抗后生利什曼病的策略。","authors":"Camila S Freitas, Daniela P Lage, Breno L Pimenta, Saulo S G Dias, Karolina O M Falcão, Isabela A G Pereira, Ana L Silva, Luciana M R Antinarelli, Raquel S B Câmara, Marcelo M Jesus, Maíza M Rodrigues, Dóris M Abrão, Grasiele S V Tavares, Miguel A Chávez-Fumagalli, Bruno A Oliveira, Myron Christodoulides, Adilson D Silva, Elaine S Coimbra, Eduardo A F Coelho","doi":"10.1016/j.actatropica.2025.107763","DOIUrl":null,"url":null,"abstract":"<p><p>Current drugs used to treat tegumentary leishmaniasis (TL) are toxic, present high cost and/or there is the emergence of resistant strains. Thus, there is requirement to identify new antileishmanial candidates and, in the present study, a 1,2,3-triazolium derivative, called Nic, was incorporated into polymeric micelles and used to treat Leishmania amazonensis-infected BALB/c mice. Animals were infected and, 60 days post-infection, they received saline, empty micelle (MIC), Nic, Nic/MIC or amphotericin B (AmpB), as drug control. At one and 30 days after therapy, animals were euthanized, and their blood samples, infected tissue and organs were collected to perform biochemical, parasitological and immunological assays. Results showed that at both time points, mice treated with Nic/MIC generated antileishmanial Th1-type cellular and humoral responses characterized by significantly higher levels (P < 0.05) of IFN-γ, IL-12, IFN-γ mRNA expression, nitrite, and IgG2a antibodies. Significant reductions in the parasite load were found by evaluating livers, spleens, draining lymph nodes and infected footpads of these animals. In addition, low levels of urea, creatinine, alanine transaminase, and aspartate transaminase were found in their sera. In conclusion, data suggest that Nic/MIC could be considered in future studies as a therapeutic candidate against TL.</p>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":" ","pages":"107763"},"PeriodicalIF":2.5000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Polymeric micelles loaded with a 1,2,3-triazolium derivative: a promising strategy against tegumentary leishmaniasis.\",\"authors\":\"Camila S Freitas, Daniela P Lage, Breno L Pimenta, Saulo S G Dias, Karolina O M Falcão, Isabela A G Pereira, Ana L Silva, Luciana M R Antinarelli, Raquel S B Câmara, Marcelo M Jesus, Maíza M Rodrigues, Dóris M Abrão, Grasiele S V Tavares, Miguel A Chávez-Fumagalli, Bruno A Oliveira, Myron Christodoulides, Adilson D Silva, Elaine S Coimbra, Eduardo A F Coelho\",\"doi\":\"10.1016/j.actatropica.2025.107763\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Current drugs used to treat tegumentary leishmaniasis (TL) are toxic, present high cost and/or there is the emergence of resistant strains. Thus, there is requirement to identify new antileishmanial candidates and, in the present study, a 1,2,3-triazolium derivative, called Nic, was incorporated into polymeric micelles and used to treat Leishmania amazonensis-infected BALB/c mice. Animals were infected and, 60 days post-infection, they received saline, empty micelle (MIC), Nic, Nic/MIC or amphotericin B (AmpB), as drug control. At one and 30 days after therapy, animals were euthanized, and their blood samples, infected tissue and organs were collected to perform biochemical, parasitological and immunological assays. Results showed that at both time points, mice treated with Nic/MIC generated antileishmanial Th1-type cellular and humoral responses characterized by significantly higher levels (P < 0.05) of IFN-γ, IL-12, IFN-γ mRNA expression, nitrite, and IgG2a antibodies. Significant reductions in the parasite load were found by evaluating livers, spleens, draining lymph nodes and infected footpads of these animals. 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Polymeric micelles loaded with a 1,2,3-triazolium derivative: a promising strategy against tegumentary leishmaniasis.
Current drugs used to treat tegumentary leishmaniasis (TL) are toxic, present high cost and/or there is the emergence of resistant strains. Thus, there is requirement to identify new antileishmanial candidates and, in the present study, a 1,2,3-triazolium derivative, called Nic, was incorporated into polymeric micelles and used to treat Leishmania amazonensis-infected BALB/c mice. Animals were infected and, 60 days post-infection, they received saline, empty micelle (MIC), Nic, Nic/MIC or amphotericin B (AmpB), as drug control. At one and 30 days after therapy, animals were euthanized, and their blood samples, infected tissue and organs were collected to perform biochemical, parasitological and immunological assays. Results showed that at both time points, mice treated with Nic/MIC generated antileishmanial Th1-type cellular and humoral responses characterized by significantly higher levels (P < 0.05) of IFN-γ, IL-12, IFN-γ mRNA expression, nitrite, and IgG2a antibodies. Significant reductions in the parasite load were found by evaluating livers, spleens, draining lymph nodes and infected footpads of these animals. In addition, low levels of urea, creatinine, alanine transaminase, and aspartate transaminase were found in their sera. In conclusion, data suggest that Nic/MIC could be considered in future studies as a therapeutic candidate against TL.
期刊介绍:
Acta Tropica, is an international journal on infectious diseases that covers public health sciences and biomedical research with particular emphasis on topics relevant to human and animal health in the tropics and the subtropics.