Generating nanoparticles containing a new 4-nitrobenzaldehyde thiosemicarbazone compound with antileishmanial activity.
Thiosemicarbazones are an important class of compounds that have been extensively studied in recent years, mainly because of their broad profile of pharmacological activity. A new 4-nitrobenzaldehyde thiosemicarbazone compound (BZTS) that was derived from S-limonene has been demonstrated to have significant antiprotozoan activity. However, the hydrophobic characteristic of BZTS limits its administration and results in low oral bioavailability. In the present study, we proposed the synthesis of nanoparticle-based block copolymers that can encapsulate BZTS, with morphological evaluation of the nanoparticle suspensions being performed by transmission and cryo-transmission electronic microscopy. The mean particle sizes of the nanoparticle suspensions were determined by static light and dynamic light scattering (SLS/DLS), and the hydrodynamic radius (Rh) was determined using the Stokes-Einstein equation. The zeta potential (ζ) and polydispersity index (PDI) were also determined. The entrapment encapsulation efficiency of the BZTS nanoparticles was measured by ultraviolet spectrophotometry. In vitro activity of BZTS nanoparticle suspensions against intracellular amastigotes of Leishmania amazonensis and cytotoxic activity were also evaluated. The results showed the production of spherical nanoparticles with varied sizes depending on the hydrophobic portion of the amphiphilic diblock copolymers used. Significant concentration-dependent inhibitory activity against intracellular amastigotes was observed, and low cytotoxic activity was demonstrated against macrophages.
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Brazil.
Elizandra Aparecida
EA
Britta
Departamento de Química, Universidade Estadual de Maringá, Brazil.
Cleuza Conceição
CC
da Silva
Departamento de Química, Universidade Estadual de Maringá, Brazil.
Adley Forti
AF
Rubira
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Brazil. Electronic address: cvnakamura@uem.br.
Celso Vataru
CV
Nakamura
Centro de Pesquisas em Macromoléculas Vegetais, CERMAV, Grenoble, France. Electronic address: borsali@cermav.cnrs.fr.
Redouane
R
Borsali
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology; D001547:Benzaldehydes / Q000737:chemistry; D002460:Cell Line; D000067493:Dynamic Light Scattering; D007891:Leishmania / Q000187:drug effects; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013056:Spectrophotometry, Ultraviolet; D013882:Thiosemicarbazones / Q000737:chemistry*
D000981:Antiprotozoal Agents; D001547:Benzaldehydes; D013882:Thiosemicarbazones; C029915:4-nitrobenzaldehyde
4-Nitrobenzaldehyde thiosemicarbazone; Antileishmanial activity; Block copolymers; Leishmania amazonensis; Nanoparticles