The focus of the present study was the monitoring of ambrisentan (AMB) in vitro biotransformation by two fungal cultures: Aspegillus niger ATCC 9029 and Penicillium mineoluteum URM 6889. This drug is a selective endothelin Type A, receptor antagonist, used for pulmonary arterial hypertension. In vitro metabolism study was carried out by incubating AMB with fungus and culture medium under controlled conditions for further analysis of metabolites formed through an alternative method. After incubation for 240 hours with A. niger , drug was metabolized into two substances: one is known (M2) with 3.75 min retention time and another unknown (M3) at 4.37 min retention time in high performance liquid chromatography–diode array detector method (HPLC‐DAD). Structures were suggested by using ultra high performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF/MS) method. When drug was submitted to biotransformation with P. mineoluteum , no different signals than those formed in the controls were observed, demonstrating it is not adequate to the purpose. The findings indicate that fungi A. niger could be used to generate mammalian metabolites of AMB on a small scale and can also be used as reference standard for identification and analytical tests of mammalian metabolites of this drug.

Our research group previously studied the effectiveness of lipid-core nanocapsules (LNC) containing simvastatin (SV-LNC) in treating cognitive impairment in rats. While our results were promising, we needed to evaluate the potential toxicity of the nanoparticles themselves. This study aimed to compare the biochemical and hematological parameters of adult Wistar rats receiving LNC or SV-LNC to those receiving low doses of simvastatin crystals dispersed in a saline solution over 45 days. We discovered that LNC and SV-LNC, which are both nanometers in size with low polydispersity index, negative zeta potential, and high SV encapsulation efficacy, were not more toxic than SV crystals based on various biochemical markers of hepatic, pancreatic, renal, mineral, bony, alkaline phosphatase, glucose, and uric acid damage. Furthermore, LNC exhibited no toxicity for hematological parameters, including red and white blood cell counts. Based on this animal model of toxicological study, our findings suggest that long-term administration of LNC is a safe and promising nanocarrier.