Article
Thermosensitive system formed by poloxamers containing carvacrol: An effective carrier system against Leishmania amazonensis
Registro en:
COSTA, Amanda Mendonça Barros et al. Acta Tropica, v. 237, p. 1-11, 106744, 2023.
0001-706X
10.1016/j.actatropica.2022.106744
Autor
Costa, Amanda Mendonça Barros
Silva, Audrey Rouse Soares Tavares
Santos, Adriana de Jesus
Galvão, Juliana Gouveia
Andrade Neto, Valter Viana
Santos, Eduardo Caio Torres
Ueki, Marcelo Massayoshi
Almeida, Luis Eduardo
Sarmento, Victor Hugo Vitorino
Dolabella, Silvio Santana
Scher, Ricardo
Lira, Ana Amélia Moreira
Nunes, Rogéria de Souza
Resumen
The drugs used in the treatment of leishmaniasis show problems concerning side effects and toxicity. As a result,
the search for new actives is necessary, and natural products like carvacrol - 5-isopropyl-2-methylphenol, become a
relevant alternative. To enable the use of carvacrol as an antileishmanial agent, thermosensitive hydrogels were
developed from poloxamer triblock copolymers 407 (P407) and 188 (P188). Carvacrol-free and carvacrolcontaining
hydrogels were obtained from P407 alone and from the mixture of P407 and P188. The hydrogels
were subjected to Differential scanning calorimetry, Small-angle X-ray scattering, Scanning electron microscopy, and
Rheology analysis. The activity of hydrogels and carvacrol isolated against promastigotes and intracellular
amastigotes of Leishmania amazonensis and their cytotoxicity in mammalian cells was determined. The sol-gel
transition temperature for the binary hydrogel containing carvacrol (HG407/188CA) was 37.04 ± 1.35 ◦C.
HG407/188CA presented lamellar structure at temperatures of 25 ◦C and 37 ◦C. HG407/188CA and carvacrol
presented IC50 against Leishmania amazonensis promastigotes of 18.68 ± 1.43 μg/mL and 23.83 ± 3.32 μg/mL,
respectively, and IC50 against Leishmania amazonensis amastigotes of 35.08 ± 0.75 μg/mL and 29.32 ± 0.21 μg/
mL, respectively. HG407/188CA reduced the toxicity of carvacrol in all mammalian cells evaluated, raising the
CC50 in murine peritoneal macrophages from 40.23 ± 0.21 μg/mL to 332.6 ± 4.89 μg/mL, obtaining a Selectivity
Index (SI) of 9.5 against 1.37 of the isolated carvacrol. HG407/188CA provided higher selectivity of carvacrol for
the parasite. Thus, the binary hydrogel obtained may enable the use of carvacrol as a potential antileishmanial
agent. 2030