Cytotoxic Screening and Enhanced Anticancer Activity of <i>Lippia alba and Clinopodium nepeta</i> Essential Oils-Loaded Biocompatible Lipid Nanoparticles against Lung and Colon Cancer Cells
Boris Rodenak-Kladniew,
María Agustina Castro,
Rocío Celeste Gambaro,
Juan Girotti,
José Sebastián Cisneros,
Sonia Viña,
Gisel Padula,
Rosana Crespo,
Guillermo Raúl Castro,
Stephan Gehring,
Cecilia Yamil Chain,
Germán Abel Islan
Affiliations
Boris Rodenak-Kladniew
INIBIOLP—Instituto de Investigaciones Bioquímicas de La Plata (UNLP-CONICET LA PLATA), Facultad de Ciencias Médicas UNLP, La Plata 1900, Argentina
María Agustina Castro
INIBIOLP—Instituto de Investigaciones Bioquímicas de La Plata (UNLP-CONICET LA PLATA), Facultad de Ciencias Médicas UNLP, La Plata 1900, Argentina
Rocío Celeste Gambaro
IGEVET—Instituto de Genética Veterinaria (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, La Plata 1900, Argentina
Juan Girotti
INIBIOLP—Instituto de Investigaciones Bioquímicas de La Plata (UNLP-CONICET LA PLATA), Facultad de Ciencias Médicas UNLP, La Plata 1900, Argentina
José Sebastián Cisneros
INIFTA—Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (UNLP-CONICET LA PLATA), La Plata 1900, Argentina
Sonia Viña
CIDCA—Centro de Investigación y Desarrollo en Criotecnología de Alimentos (UNLP-CONICET LA PLATA), Facultad de Ciencias Exactas UNLP, La Plata 1900, Argentina
Gisel Padula
IGEVET—Instituto de Genética Veterinaria (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, La Plata 1900, Argentina
Rosana Crespo
IFEC—Instituto de Farmacología Experimental de Córdoba (UNC-CONICET UNC), Facultad de Ciencias Químicas UNC, Córdoba 5000, Argentina
Guillermo Raúl Castro
Nanomedicine Research Unit (Nanomed), Center for Natural and Human Sciences (CCNH), Universidade Federal do ABC (UFABC), Santo André 09210-580, Brazil
Stephan Gehring
Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany
Cecilia Yamil Chain
INIFTA—Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (UNLP-CONICET LA PLATA), La Plata 1900, Argentina
Germán Abel Islan
Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany
Plant and herbal essential oils (EOs) offer a wide range of pharmacological actions that include anticancer effects. Here, we evaluated the cytotoxic activity of EO from Lippia alba (chemotype linalool), L. alba (chemotype dihydrocarvone, LaDEO), Clinopodium nepeta (L.) Kuntze (CnEO), Eucalyptus globulus, Origanum × paniculatum, Mentha × piperita, Mentha arvensis L., and Rosmarinus officinalis L. against human lung (A549) and colon (HCT-116) cancer cells. The cells were treated with increasing EO concentrations (0–500 µL/L) for 24 h, and cytotoxic activity was assessed. LaDEO and CnEO were the most potent EOs evaluated (IC50 range, 145–275 µL/L). The gas chromatography–mass spectrometry method was used to determine their composition. Considering EO limitations as therapeutic agents (poor water solubility, volatilization, and oxidation), we evaluated whether LaDEO and CnEO encapsulation into solid lipid nanoparticles (SLN/EO) enhanced their anticancer activity. Highly stable spherical SLN/LaDEO and SLN/CnEO SLN/EO were obtained, with a mean diameter of 140–150 nm, narrow size dispersion, and Z potential around −5mV. EO encapsulation strongly increased their anticancer activity, particularly in A549 cells exposed to SLN/CnEO (IC50 = 66 µL/L CnEO). The physicochemical characterization, biosafety, and anticancer mechanisms of SLN/CnEO were also evaluated in A549 cells. SLN/CnEO containing 97 ± 1% CnEO was highly stable for up to 6 months. An increased in vitro CnEO release from SLN at an acidic pH (endolysosomal compartment) was observed. SLN/CnEO proved to be safe against blood components and non-toxic for normal WI-38 cells at therapeutic concentrations. SLN/CnEO substantially enhanced A549 cell death and cell migration inhibition compared with free CnEO.
