학술논문
Effect of 3-Carene and the Micellar Formulation on Leishmania (Leishmania) amazonensis
Document Type
Academic Journal
Author
Source
Tropical Medicine and Infectious Disease. June 2023, Vol. 8 Issue 6
Subject
Language
English
ISSN
2414-6366
Abstract
Author(s): Audrey Rouse Soares Tavares Silva [1]; Amanda Mendonça Barros Costa [1]; Ricardo Scher [2]; Valter Viana Andrade-Neto [3]; Victor Hugo Vitorino Sarmento [4]; Adriana de Jesus Santos [1]; Eduardo [...]
Leishmaniases are neglected tropical diseases caused by obligate intracellular protozoa of the genus Leishmania. The drugs used in treatment have a high financial cost, a long treatment time, high toxicity, and variable efficacy. 3-Carene (3CR) is a hydrocarbon monoterpene that has shown in vitro activity against some Leishmania species; however, it has low water solubility and high volatility. This study aimed to develop Poloxamer 407 micelles capable of delivering 3CR (P407-3CR) to improve antileishmanial activity. The micelles formulated presented nanometric size, medium or low polydispersity, and Newtonian fluid rheological behavior. 3CR and P407-3CR inhibited the growth of L. (L.) amazonensis promastigote with IC[sub.50]/48h of 488.1 ± 3.7 and 419.9 ±1.5 mM, respectively. Transmission electron microscopy analysis showed that 3CR induces multiple nuclei and kinetoplast phenotypes and the formation of numerous cytosolic invaginations. Additionally, the micelles were not cytotoxic to L929 cells or murine peritoneal macrophages, presenting activity on intracellular amastigotes. P407-3CR micelles (IC[sub.50]/72 h = 0.7 ± 0.1 mM) increased the monoterpene activity by at least twice (3CR: IC[sub.50]/72 h >1.5 mM). These results showed that P407 micelles are an effective nanosystem for delivering 3CR and potentiating antileishmanial activity. More studies are needed to evaluate this system as a potential therapeutic option for leishmaniases.
Leishmaniases are neglected tropical diseases caused by obligate intracellular protozoa of the genus Leishmania. The drugs used in treatment have a high financial cost, a long treatment time, high toxicity, and variable efficacy. 3-Carene (3CR) is a hydrocarbon monoterpene that has shown in vitro activity against some Leishmania species; however, it has low water solubility and high volatility. This study aimed to develop Poloxamer 407 micelles capable of delivering 3CR (P407-3CR) to improve antileishmanial activity. The micelles formulated presented nanometric size, medium or low polydispersity, and Newtonian fluid rheological behavior. 3CR and P407-3CR inhibited the growth of L. (L.) amazonensis promastigote with IC[sub.50]/48h of 488.1 ± 3.7 and 419.9 ±1.5 mM, respectively. Transmission electron microscopy analysis showed that 3CR induces multiple nuclei and kinetoplast phenotypes and the formation of numerous cytosolic invaginations. Additionally, the micelles were not cytotoxic to L929 cells or murine peritoneal macrophages, presenting activity on intracellular amastigotes. P407-3CR micelles (IC[sub.50]/72 h = 0.7 ± 0.1 mM) increased the monoterpene activity by at least twice (3CR: IC[sub.50]/72 h >1.5 mM). These results showed that P407 micelles are an effective nanosystem for delivering 3CR and potentiating antileishmanial activity. More studies are needed to evaluate this system as a potential therapeutic option for leishmaniases.