Formulation and characterization of solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsion of lornoxicam for transdermal delivery

Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsion (NE) of lornoxicam (LRX) were prepared for the treatment of painful and inflammatory conditions of skin. Compritol® 888 ATO, Lanette® O and oleic acid were used as solid and liquid lipids. Nanoparticles and nanoemulsion were obtained in a range 141 to 295 nm diameter (D50). 185 nm and 295 nm particle sizes were obtained for SLN of LRX based on Compritol® 888 ATO and Lanette® O when NLC displayed 185 nm and 266 nm particle sizes, respectively. Droplet size of drug NE was 166 nm. They were found physically stable at various temperatures for 6 months. Case I diffusional drug release was detected as the dominant mechanism indicating Fickian drug diffusion from nanoparticles and nanoemulsion. The highest rate of drug penetration through rat skin was obtained with NE followed by NLC, SLN and a gel formulation. Nanoformulations significantly increased drug penetration through rat skin compared to the gel (p < 0.05). Thus, SLN, NLC and NE of LRX can be suggested for relieving painful and inflammatory conditions of the skin by sustained drug release

Alterations in global DNA methylation and metabolism-related genes caused by zearalenone in MCF7 and MCF10F cells

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by Fusarium fungi. ZEN has endocrine disruptor effects and could impair the hormonal balance. Here, we aimed at investigating possible effects of ZEN on metabolism-related pathways and its relation to epigenetic mechanisms in breast adenocarcinoma (MCF7) and breast epithelial (MCF10F) cells. Using the MTT and neutral red uptake (NRU) cell viability tests, IC50 values of ZEN after 24h were found to be 191 mu mol/L and 92.6 mu mol/L in MCF7 cells and 67.4 mu mol/L and 79.5 mu mol/L in MCF10F cells. A significant increase on global levels of 5-methylcytosine (5-mC%) was observed for MCF7 cells, correlating with the increased expression of DNA methyltransferases. No alterations were observed on levels of 5-mC% and expression of DNA methyltransferases for MCF10F cells. Further, at least threefold upregulation compared to control was observed for several genes related to nuclear receptors and metabolism in MCF7 cells, while some of these genes were downregulated in MCF10F cells. The most notably altered genes were IGF1, HK2, PXR, and PPAR gamma. We suggested that ZEN could alter levels of global DNA methylation and impair metabolism-related pathways