sirolimus and 1-2-distearoylphosphatidylethanolamine

Atherosclerosis (AS) is one of the leading causes of vascular disease, producing high morbidity and mortality in many countries. Autophagy plays an important role when cells are facing serious circumstances, such as oxidative stress induced by Ox-LDL (oxidized low-density lipoprotein). Recent studies have revealed that DEX (dexamethasone acetate) and RAPA (rapamycin) exhibit efficient AS therapeutic ability by protecting endothelial cells and killing foam cells, respectively. Herein, we hypothesize that combining DEX and RAPA together in a specific nanocarrier system can achieve better AS therapy while limiting harmful effects. As a proof of concept, DEX and RAPA coloaded mPEG

Topics: Animals; Atherosclerosis; Autophagy; Calcium Phosphates; Dexamethasone; Endothelial Cells; Lipoproteins, LDL; Mice; Nanoparticles; Phosphatidylethanolamines; Sirolimus

Rapamycin and 5-fluorocytosine (5-FC) are antifungal agents with unique mechanisms of activity, with potential for cooperative interaction with AmB. Combination antifungal therapy involving conventional AmB has been restricted by poor physical stability and compatibility with antifungal drugs and vehicles.. AmB and rapamycin were encapsulated in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy poly(ethylene glycol) (PEG-DSPE) micelles using a solvent evaporation method. The physical stability of micelle encapsulated AmB and rapamycin with 5-FC and saline was evaluated using dynamic light scattering (DLS). In vitro susceptibility of Candida albicans isolates to 5-FC and PEG-DSPE micelle solubilized AmB and rapamycin has been evaluated. Interactive effects have been quantified using a checkerboard layout.. In contrast with conventional AmB, PEG-DSPE micelles encapsulating AmB and rapamycin are compatible with saline and 5-FC over 12 h. The solubilized drugs retain high level of potency in vitro. The combination of solubilized AmB and rapamycin was indifferent, as fractional inhibitory concentration (FIC) index and combination index (CI) values were approximately 1. Combinations of solubilized AmB or rapamycin with 5-FC, and the three-drug combination were moderately synergistic since the FIC index and CI values were consistent less than 1.. These results indicate that AmB solubilized in PEG-DSPE micelles is compatible with solubilized rapamycin and 5-FC. The indifferent or moderately synergistic activity of combinations is encouraging and warrants further investigation in appropriate rodent models.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Chemistry, Pharmaceutical; Drug Carriers; Drug Combinations; Drug Stability; Drug Synergism; Flucytosine; Micelles; Microbial Sensitivity Tests; Phosphatidylethanolamines; Polyethylene Glycols; Sirolimus; Solubility; Technology, Pharmaceutical