| Author | Galvão, Juliana G. | |
| Author | Santos, Raquel L. | |
| Author | Silva, Audrey R. S. T. | |
| Author | Santos, Jeferson S. | |
| Author | Costa, Amanda M. B. | |
| Author | Chandasana, Hardik | |
| Author | Andrade Neto, Valter V. | |
| Author | Santos, Eduardo Caio Torres | |
| Author | Lira, Ana Amélia M. | |
| Author | Dolabella, Silvio | |
| Author | Scher, Ricardo | |
| Author | Kima, Peter E. | |
| Author | Derendorf, Hartmut | |
| Author | Nunes, Rogéria S. | |
| Access date | 2020-07-25T19:19:00Z | |
| Available date | 2020-07-25T19:19:00Z | |
| Document date | 2020 | |
| Citation | GALVÃO, Juliana G. et al. Carvacrol loaded nanostructured lipid carriers as a promising parenteral formulation for leishmaniasis treatment. European Journal of Pharmaceutical Sciences, v. 150, p. 1-12, Apr. 2020. | pt_BR |
| ISSN | 0928-0987 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/42398 | |
| Language | eng | pt_BR |
| Publisher | Elsevier 12 Months | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Leishmania | pt_BR |
| Subject in Portuguese | Lipídios sólidos | pt_BR |
| Subject in Portuguese | Monoterpeno fenólico | pt_BR |
| Subject in Portuguese | Produtos naturais | pt_BR |
| Subject in Portuguese | Nanomedicina | pt_BR |
| Subject in Portuguese | Tratamento intravenoso | pt_BR |
| Title | Carvacrol loaded nanostructured lipid carriers as a promising parenteral formulation for leishmaniasis treatment | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.ejps.2020.105335 | |
| Abstract | 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. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Farmácia. São Cristóvão, SE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Farmácia. São Cristóvão, SE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Morfologia. São Cristóvao. SE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Farmácia. São Cristóvão, SE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Farmácia. São Cristóvão, SE, Brasil. | pt_BR |
| Affilliation | University of Florida, Department of Pharmaceutics. FL, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Farmácia. São Cristóvão, SE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Morfologia. São Cristóvao. SE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Morfologia. São Cristóvao. SE, Brasil. | pt_BR |
| Affilliation | University of Florida. Department of Microbiology and Cell Science. FL, USA. | pt_BR |
| Affilliation | University of Florida, Department of Pharmaceutics. FL, USA. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Farmácia. São Cristóvão, SE, Brasil. | pt_BR |
| Subject | Solid lipids | pt_BR |
| Subject | Phenolic monoterpene | pt_BR |
| Subject | Natural products | pt_BR |
| Subject | Leishmania | pt_BR |
| Subject | Nanomedicine | pt_BR |
| Subject | Intravenous treatment | pt_BR |
| e-ISSN | 1879-0720 | |
