Morphological and biological properties of silica nanoparticles for CRTC3-siRNA delivery and downregulation of the RGS2 expression in preadipocytes.

The aim of this study was to characterize the morphological properties of amorphous silica nanoparticles (SiO2 NPs), their cytotoxicity and intracellular location within Human Osteoblasts (HOB). Additionally, SiO2 NPs were explored for their effectivity as carriers of CRTC3-siRNA on Human Preadipocytes (HPAd), and thus downregulate RGS2 gene expression. SiO2 NPs were synthesized using the method of Stöber at 45 °C, 56 °C, and 62 °C. These were characterized via TEM with EDS, Zeta Potential and FT-IR. Cytotoxicity was evaluated by XTT at three concentrations 50, 100 and 500 µg/mL; SiO2 NPs intracellular localization was observed through Confocal Laser Scanning Microscope. Delivering siRNA effectivity was measured by RT-qPCR. Morphology of SiO2 NPs was spherical with a range size from 64 to 119 nm; their surface charge was negative. Confocal images demonstrated that SiO2 NPs were located within cellular cytoplasm. At a SiO2 NPs concentration of 500 µg/mL HOB viability decreased, while at 50 µg/mL and 100 µg/mL cell viability was not affected regardless SiO2 NPs size. SiO2 NPs-CRTC3-siRNA are effective to down-regulate RGS2 gene expression in HPAd without cytotoxic effects. The developed SiO2 NPs-CRTC3-siRNA are a promising tool as a delivery vehicle to control obesity.

Absence of a significant pharmacokinetic interaction between atorvastatin and fenofibrate: a randomized, crossover, study of a fixed-dose formulation in healthy Mexican subjects.

Several clinical trials have substantiated the efficacy of the co-administration of statins like atorvastatin (ATO) and fibrates. Without information currently available about the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the effect when both drugs were co-administered. The purpose of this study was to investigate the pharmacokinetic profile of tablets containing ATO 20 mg, or the combination of ATO 20 mg with fenofibrate (FNO) 160 mg administered to healthy Mexican volunteers. This was a randomized, two-period, two-sequence, crossover study; 36 eligible subjects aged between 20-50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by non-compartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC) and maximum plasma drug concentration (Cmax) were measured for ATO as the reference and ATO and FNO as the test product for bioequivalence design. The estimation computed (90% confidence intervals) for ATO and FNO combination versus ATO for Cmax, AUC0-t and AUC0-∞, were 102,09, 125,95, and 120,97%, respectively. These results suggest that ATO and FNO have no relevant clinical-pharmacokinetic drug interaction.