RESUMEN
Leishmaniases, a group of neglected tropical diseases caused by an intracellular parasite of the genus Leishmania, have significant impacts on global health. Current treatment options are limited due to drug resistance, toxicity, and high cost. This study aimed to develop nanostructured lipid carriers (NLCs) for delivering Citrus sinensis essential oil (CSEO) and its main constituent, R-limonene, against leishmaniasis. The influence of surface-modified NLCs using chitosan was also examined. The NLCs were prepared using a warm microemulsion method, and surface modification with chitosan was achieved through electrostatic interaction. These nanocarriers were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), transmission electron microscopy, and dynamic light scattering (DLS). In vitro cytotoxicity was assessed in L929 and RAW 264.7 cells, and leishmanicidal activity was evaluated against promastigote and amastigote forms. The NLCs were spherical, with particle sizes ranging from 97.9 nm to 111.3 nm. Chitosan-coated NLCs had a positive surface charge, with zeta potential values ranging from 45.8 mV to 59.0 mV. Exposure of L929 cells to NLCs resulted in over 70 % cell viability. Conversely, surface modification significantly reduced the viability of promastigotes (93 %) compared to free compounds. Moreover, chitosan-coated NLCs presented a better IC50 against the amastigote forms than uncoated NLCs. Taken together, these findings demonstrate the feasibility of using NLCs to overcome the limitations of current leishmaniasis treatments, warranting further research.
Asunto(s)
Supervivencia Celular , Quitosano , Citrus sinensis , Portadores de Fármacos , Limoneno , Lípidos , Nanopartículas , Aceites Volátiles , Aceites Volátiles/administración & dosificación , Aceites Volátiles/química , Aceites Volátiles/farmacología , Animales , Ratones , Limoneno/química , Limoneno/administración & dosificación , Limoneno/farmacología , Portadores de Fármacos/química , Células RAW 264.7 , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Quitosano/administración & dosificación , Lípidos/química , Lípidos/administración & dosificación , Nanopartículas/química , Nanopartículas/administración & dosificación , Citrus sinensis/química , Antiprotozoarios/administración & dosificación , Antiprotozoarios/farmacología , Antiprotozoarios/química , Leishmaniasis/tratamiento farmacológico , Tamaño de la Partícula , Línea Celular , Leishmania/efectos de los fármacos , Terpenos/química , Terpenos/farmacología , Terpenos/administración & dosificación , Nanoestructuras/química , Nanoestructuras/administración & dosificaciónRESUMEN
Hancornia speciosa Gomes (HS) is a Brazilian fruit tree used in inflammatory disorders by folk medicine. Here we sought to investigate the antioxidant and hepatoprotective properties of HS fruit juice in acetaminophen-induced hepatoxicity model in rats, as well as to perform a comprehensive chemical characterization of phenolics and metals by mass spectrometry. HS showed hepatoprotective and antioxidant activity by decreasing MDA and liver injury markers at healthy control levels. In addition, liver histopathological analysis revealed that HS decreases hepatocellular degeneration. Chemical characterization revealed 16 different phenolics, being chlorogenic acid (150 ± 5 µg/g) and rutin (120 ± 8 µg/g) the major phenolics in HS. Among the 14 micronutrients we identified, zinc and boron were the most abundant metals detected in HS. In line with previous studies involving liver diseases, our data supports evidence that such phenolics and metals present in HS may prevent liver injury induced by acetaminophen.
Asunto(s)
Apocynaceae , Enfermedad Hepática Inducida por Sustancias y Drogas , Acetaminofén/toxicidad , Animales , Antioxidantes/farmacología , Apocynaceae/química , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Jugos de Frutas y Vegetales , Hígado , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , RatasRESUMEN
Leishmaniasis are a group of neglected infectious diseases caused by protozoa of the genus Leishmania with distinct presentations. The available leishmaniasis treatment options are either expensive and/or; cause adverse effects and some are ineffective for resistant Leishmania strains. Therefore, molecules derived from natural products as the monoterpene carvacrol, have attracted interest as promising anti-leishmania agents. However, the therapeutic use of carvacrol is limited due to its low aqueous solubility, rapid oxidation and volatilization. Thus, the development of nanostructured lipid carriers (NLCs) was proposed in the present study as a promising nanotechnology strategy to overcome these limitations and enable the use of carvacrol in leishmaniasis therapy. Carvacrol NLCs were obtained using a warm microemulsion method, and evaluated regarding the influence of lipid matrix and components concentration on the NLCs formation. NLCs were characterized by DSC and XRD as well. In addition, to the in vitro carvacrol release from NLCs, the in vitro cytotoxicity and leishmanicidal activity assays, and the in vivo pharmacokinetics evaluation of free and encapsulated carvacrol were performed. NLCs containing carvacrol were obtained successfully using a warm microemulsion dilution method. The NLCs formulation with the lowest particle size (98.42 ± 0.80 nm), narrowest size distribution (suitable for intravenous administration), and the highest encapsulation efficiency was produced by using beeswax as solid lipid (HLB=9) and 5% of lipids and surfactant. The in vitro release of carvacrol from NLCs was fitted to the Korsmeyer and Peppas, and Weibull models, demonstrating that the release mechanism is probably the Fickian diffusion type. Moreover, carvacrol encapsulation in NLCs provided a lower cytotoxicity in comparison to free carvacrol (p<0.05), increasing its in vitro leishmanicidal efficacy in the amastigote form. Finally, the in vivo pharmacokinetics of carvacrol after IV bolus administration suggests that this phenolic monoterpene undergoes enterohepatic circulation and therefore presented a long half-life (t1/2) and low clearance (Cl). In addition, C0, mean residence time (MRT) and Vdss of encapsulated carvacrol were higher than free carvacrol (p < 0.05), favoring a higher distribution of carvacrol in the target tissues. Thus, it is possible to conclude that the developed NLCs are a promising delivery system for leishmaniasis treatment.
Asunto(s)
Antiprotozoarios/administración & dosificación , Cimenos/administración & dosificación , Portadores de Fármacos/administración & dosificación , Leishmania/efectos de los fármacos , Nanoestructuras/administración & dosificación , Animales , Antiprotozoarios/sangre , Antiprotozoarios/química , Antiprotozoarios/farmacocinética , Supervivencia Celular/efectos de los fármacos , Cimenos/sangre , Cimenos/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberación de Fármacos , Humanos , Leishmaniasis/tratamiento farmacológico , Lípidos/administración & dosificación , Lípidos/química , Lípidos/farmacocinética , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Ratones Endogámicos BALB C , Nanoestructuras/química , Ratas Wistar , Células THP-1RESUMEN
Several constituents of essential oils have been shown to be active against pathogens such as bacteria, fungi, and protozoa. This study demonstrated the in vitro action of ten compounds present in essential oils against Leishmania amazonensis promastigotes. With the exception of p-cymene, all evaluated compounds presented leishmanicidal activity, exhibiting IC50 between 25.4 and 568.1 µg mL-1. Compounds with the best leishmanicidal activity presented a phenolic moiety (IC50 between 25.4 and 82.9 µg mL-1). Alicyclic alcohols ((-)-menthol and isoborneol) and ketones ((-)-carvone) promoted similar activity against the parasite (IC50 between 190.2 and 198.9 µg mL-1). Most of the compounds showed low cytotoxicity in L929 fibroblasts. Analysis of the structure-activity relationship of these compounds showed the importance of the phenolic structure for the biological action against the promastigote forms of the parasite.