The development of drug carriers based in lipid nanoparticles (LNPs) aims toward the synthesis of non-toxic multifunctional nanovehicles that can bypass the immune system and allow specific site targeting, controlled release and complete degradation of the carrier components. Among label free techniques, Surface Plasmon Resonance (SPR) biosensing is a versatile tool to study LNPs in the field of nanotherapeutics research. SPR, widely used for the analysis of molecular interactions, is based on the immobilization of one of the interacting partners to the sensor surface, which can be easily achieved in the case of LNPs by hydrophobic attachment onto commercial lipid- capture sensor chips. In the last years SPR technology has emerged as an interesting strategy for studying molecular aspects of drug delivery that determines the efficacy of the nanotherapeutical such as LNPs' interactions with biological targets, with serum proteins and with tumor extracelullar matrix. Moreover, SPR has contributed to the obtention and characterization of LNPs, gathering information about the interplay between components of the formulations, their response to organic molecules and, more recently, the quantification and molecular characterization of exosomes. By the combination of available sensor platforms, assay quickness and straight forward platform adaptation for new carrier systems, SPR is becoming a high throughput technique for LNPs' characterization and analysis.
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.
10 January 2023 in Journal of Drug Delivery Science and Technology
Assembly and stabilization of a glutathione-complexed [2Fe–2S] cluster is promoted by aggregation of glutathione. The cluster core selects the tetramer species from a collection of equilibrating solution aggregate species, and in turn the core is stabilized toward hydrolytic degradation. Studies of glutathione derivatives, in combination with mass spectrometric and Mössbauer investigations provide insight on reaction intermediates during formation of [2Fe–2S](GS)42−.