Encapsulation of Citrus sinensis essential oil and R-limonene in lipid nanocarriers: A potential strategy for the treatment of leishmaniasis

• Published in: International journal of pharmaceutics Vol. 662; p. 124464
• Main Authors: Santos, Jeferson S., Galvão, Juliana G., Mendonça, Marcos R.C., Costa, Amanda M.B., Silva, Audrey R.S.T., Oliveira, Daniela S., Santos, Adriana de J., Lira, Ana Amélia M., Scher, Ricardo, Sales Júnior, Policarpo Ademar, Pereira, Valéria Rêgo Alves, Formiga, Fábio Rocha, Nunes, Rogéria S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.09.2024
• Subjects: Animals; Antiprotozoal Agents - administration & dosage; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Cell Line; Cell Survival - drug effects; Chitosan; Chitosan - administration & dosage; Chitosan - chemistry; Citrus sinensis - chemistry; Drug Carriers - chemistry; Essential Oil; Leishmania; Leishmania - drug effects; Leishmaniasis - drug therapy; Limonene - administration & dosage; Limonene - chemistry; Limonene - pharmacology; Lipids - administration & dosage; Lipids - chemistry; Mice; Monoterpene; Nanocarriers; Nanomedicine; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanostructures - administration & dosage; Nanostructures - chemistry; Oils, Volatile - administration & dosage; Oils, Volatile - chemistry; Oils, Volatile - pharmacology; Particle Size; RAW 264.7 Cells; Surface Modification; Terpenes - administration & dosage; Terpenes - chemistry; Terpenes - pharmacology; Leishmania; Surface Modification; Monoterpene; Essential Oil; Chitosan; Nanocarriers; Nanomedicine
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124464

[Display omitted] 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.