TY - JOUR
T1 - A Pluronic® F127-based polymeric micelle system containing an antileishmanial molecule is immunotherapeutic and effective in the treatment against Leishmania amazonensis infection
AU - Tavares, Grasiele S.V.
AU - Mendonça, Débora V.C.
AU - Miyazaki, Carolina K.
AU - Lage, Daniela P.
AU - Soyer, Tauane G.
AU - Carvalho, Lívia M.
AU - Ottoni, Flaviano M.
AU - Dias, Daniel S.
AU - Ribeiro, Patrícia A.F.
AU - Antinarelli, Luciana M.R.
AU - Ludolf, Fernanda
AU - Duarte, Mariana C.
AU - Coimbra, Elaine S.
AU - Chávez-Fumagalli, Miguel A.
AU - Roatt, Bruno M.
AU - Menezes-Souza, Daniel
AU - Barichello, José Mário
AU - Alves, Ricardo J.
AU - Coelho, Eduardo A.F.
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/2
Y1 - 2019/2
N2 - Clioquinol (5-chloro-7-iodoquinolin-8-ol or ICHQ) was recently showed to presents an in vitro effective antileishmanial action, causing changes in membrane permeability, mitochondrial functionality, and parasite morphology. In the present study, ICHQ was incorporated into a Poloxamer 407-based polymeric micelles system (ICHQ/M), and its antileishmanial activity was in vivo evaluated in L. amazonensis-infected BALB/c mice. Amphotericin B (AmpB) and its liposomal formulation (Ambisome®) were used as controls. Parasitological and immunological evaluations were performed 30 days after the treatment. Results indicated more significant reductions in the average lesion diameter and parasite burden in ICHQ or ICHQ/M-treated mice, which were associated with the development of a polarized Th1 immune response, based on production of high levels of IFN-γ IL-12, TNF-α GM-CSF, and antileishmanial IgG2a antibody. Control groups´ mice produced high levels of IL-4, IL-10, and IgG1 isotype antibody. No organic toxicity was found by using ICHQ or ICHQ/M to treat the animals, although those receiving AmpB and Ambisome® have presented higher levels of renal and hepatic damage markers. In conclusion, results suggested that the ICHQ/M composition can be considered as an antileishmanial candidate to be tested against human leishmaniasis.
AB - Clioquinol (5-chloro-7-iodoquinolin-8-ol or ICHQ) was recently showed to presents an in vitro effective antileishmanial action, causing changes in membrane permeability, mitochondrial functionality, and parasite morphology. In the present study, ICHQ was incorporated into a Poloxamer 407-based polymeric micelles system (ICHQ/M), and its antileishmanial activity was in vivo evaluated in L. amazonensis-infected BALB/c mice. Amphotericin B (AmpB) and its liposomal formulation (Ambisome®) were used as controls. Parasitological and immunological evaluations were performed 30 days after the treatment. Results indicated more significant reductions in the average lesion diameter and parasite burden in ICHQ or ICHQ/M-treated mice, which were associated with the development of a polarized Th1 immune response, based on production of high levels of IFN-γ IL-12, TNF-α GM-CSF, and antileishmanial IgG2a antibody. Control groups´ mice produced high levels of IL-4, IL-10, and IgG1 isotype antibody. No organic toxicity was found by using ICHQ or ICHQ/M to treat the animals, although those receiving AmpB and Ambisome® have presented higher levels of renal and hepatic damage markers. In conclusion, results suggested that the ICHQ/M composition can be considered as an antileishmanial candidate to be tested against human leishmaniasis.
KW - 5-chloro-7-iodoquinolin-8-ol
KW - Delivery systems
KW - Toxicity
KW - Treatment
KW - Visceral leishmaniasis
UR - http://www.scopus.com/inward/record.url?scp=85055325933&partnerID=8YFLogxK
U2 - 10.1016/j.parint.2018.10.005
DO - 10.1016/j.parint.2018.10.005
M3 - Article
C2 - 30339837
AN - SCOPUS:85055325933
SN - 1383-5769
VL - 68
SP - 63
EP - 72
JO - Parasitology International
JF - Parasitology International
IS - 1
ER -