Enhanced anticancer activity of encapsulated geraniol into biocompatible lipid nanoparticles against A549 human lung cancer cells

Geraniol (GOH) is a linear monoterpene alcohol found in essential oils of plants and herbs with multiple pharmacological properties, including anticancer activity. Due to its poor water solubility and volatility, GOH stability, administration, and bioavailability in physiological conditions should be improved to develop efficient carrier systems. Thus, GOH was encapsulated into nanostructured lipid carriers (NLC) as a novel strategy to improve its anticancer activity. Highly stable and lowly dispersed GOH-loaded NLC (NLC/GOH); 110 nm mean size, polydispersity index ([PDI] < 0.2), Zeta potential around-10mV, and 95% GOH encapsulation efficiency were obtained. After GOH inclusion, the crystallographic structure of NLC changed according to wide-and small -angle X-ray scattering studies. An increased in vitro GOH release from NLC at acidic pH (tumoral environment) after 24 h was observed. The NLC/GOH proved to be safe against blood components, adsorbed in vitro a thin layer of serum proteins, and preferentially interacted with human serum albumin compared with plasmatic opsonins. An efficient time-dependent cellular uptake of NLC/GOH was observed in A549 cells after 24 h. The A549 cell viability loss was increased (1.8-3.2 fold) after GOH encapsulation into NLC, which also enhanced mitochondrial membrane depolarization and cell death. Highly cytotoxic concentrations of NLC/GOH against A549 cells resulted non-toxic to normal lung fibroblasts WI-38 cells. Finally, GOH nanoencapsulation into NLC potentiated the inhibition of A549 cell migration exerted by free GOH.

Automated summary

Geraniol (GOH), a monoterpene alcohol found in essential oils, was encapsulated into nanostructured lipid carriers (NLC) to improve its anticancer activity. The NLC/GOH exhibited high stability and low dispersity, and showed increased release of GOH at acidic pH. The NLC/GOH were safe, absorbed serum proteins, and preferentially interacted with human serum albumin. A time-dependent cellular uptake of NLC/GOH was observed in A549 cells, leading to increased cytotoxicity, mitochondrial membrane depolarization, and cell death. NLC/GOH showed highly cytotoxic concentrations against A549 cells but was non-toxic to normal lung fibroblasts. Additionally, GOH nanoencapsulation into NLC potentiated the inhibition of A549 cell migration.