Treatment using vanillin-derived synthetic molecules incorporated into polymeric micelles is effective against infection caused by Leishmania amazonensis species

• Published in: Experimental parasitology 2024-05, Vol.260, p.108743-108743, Article 108743
• Main Authors: Pereira, Isabela A.G., Freitas, Camila S., Câmara, Raquel S.B., Jesus, Marcelo M., Lage, Daniela P., Tavares, Grasiele S.V., Soyer, Tauane G., Ramos, Fernanda F., Soares, Nícia P., Santiago, Samira S., Martins, Vívian T., Vale, Danniele L., Pimenta, Breno L., Ludolf, Fernanda, Oliveira, Fabrício M., Duarte, Mariana C., Chávez-Fumagalli, Miguel A., Costa, Adilson V., Gonçalves, Denise U., Roatt, Bruno M., Teixeira, Róbson R., Coelho, Eduardo A.F.
• Format: Article
• Language: English
• Subjects: alanine transaminase; Amphotericin B; Amphotericin B - pharmacology; Amphotericin B - therapeutic use; Animals; antileishmanial properties; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; aspartate transaminase; Benzaldehydes - chemistry; Benzaldehydes - pharmacology; creatinine; Female; immune response; immunoglobulin G; interleukin-12; Leishmania amazonensis; Leishmania infantum; Leishmania mexicana - drug effects; leishmaniasis; Leishmaniasis, Cutaneous - drug therapy; Male; Mice; Mice, Inbred BALB C; Micelles; nitrites; parasite load; parasites; parasitology; Poloxamer - chemistry; Poloxamer - pharmacology; Polymeric micelles; polymers; species; Spleen - parasitology; Tegumentary leishmaniasis; therapeutics; Treatment; urea; Vanillin
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2024.108743

Treatment against leishmaniasis presents problems, mainly due to the toxicity of the drugs, high cost, and the emergence of resistant strains. A previous study showed that two vanillin-derived synthetic molecules, 3s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], presented antileishmanial activity against Leishmania infantum, L. amazonensis, and L. braziliensis species. In the present work, 3s and 3t were evaluated to treat L. amazonensis-infected mice. Molecules were used pure or incorporated into Poloxamer 407-based micelles. In addition, amphotericin B (AmpB) and its liposomal formulation, Ambisome®, were used as control. Animals received the treatment and, one and 30 days after, they were euthanized to evaluate immunological, parasitological, and biochemical parameters. Results showed that the micellar compositions (3s/Mic and 3t/Mic) induced significant reductions in the lesion mean diameter and parasite load in the infected tissue and distinct organs, as well as a specific and significant antileishmanial Th1-type immune response, which was based on significantly higher levels of IFN-γ, IL-12, nitrite, and IgG2a isotype antibodies. Drug controls showed also antileishmanial action; although 3s/Mic and 3t/Mic have presented better and more significant parasitological and immunological data, which were based on significantly higher IFN-γ production and lower parasite burden in treated animals. In addition, significantly lower levels of urea, creatinine, alanine transaminase, and aspartate transaminase were found in mice treated with 3s/Mic and 3t/Mic, when compared to the others. In conclusion, results suggest that 3s/Mic and 3t/Mic could be considered as therapeutic candidates to treat against L. amazonensis infection. [Display omitted] •Two vanillin-derived synthetic molecules were evaluated against L. amazonensis.•Infected mice were treated with them pure or incorporated into polymeric micelles.•The compositions induced more significant reductions in the parasitism in treated animals.•A specific Th1-type humoral and cellular response was found in treated mice.•More significant therapeutic action was found when micelle-based compositions were used.