Controlled and cellulose eco-friendly synthesis and characterization of Bi2O2CO3 quantum dot nanostructures (QDNSs) and drug delivery study.

This work aimed to prepare solvent-free or green Bi2O2CO3 for quantum dot nanostructures (QDNSs) based on cellulose as a stabilizer and green capping agent to sorafenib delivery for liver targeting. Because the walnut tree is one of the most abundant trees in Iran, it was tried to synthesize Bi2O2CO3 QDNSs using a walnut skin extract. The saturation magnetization for Bi2O2CO3 QDNSs was calculated to be 68.1. Also, the size of products was measured at around 60-80 nm with the Debye-Scherrer equation. Moreover, the morphology, functional groups, and crystallography of the Bi2O2CO3 nanoparticles were investigated using atomic force microscopy, scanning electron microscopy, vibrating-sample magnetometer, and Uv-vis spectroscopy. The results demonstrated that Bi2O2CO3 QDNSs have opto-magnetic properties and they can be suggested as the candidate materials for the sorafenib delivery on the liver tissue. The optical band gap estimated for Bi2O2CO3 QDNSs was found to be red-shift from 3.22 eV. This study suggests the preparation of the Bi2O2CO3 QDNSs based on cellulose as new opto-magnetic materials at different temperatures of 180 °C, 200 °C, 220 °C, and 240 °C for sorafenib delivery as a type of biological therapy drug.

A LC-MS/MS method for therapeutic drug monitoring of sorafenib, regorafenib and their active metabolites in patients with hepatocellular carcinoma.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of sorafenib (SORA), its N-oxide active metabolite and of regorafenib (REGO) and its two active metabolites regorafenib N-oxide and N-desmethyl regorafenib N-oxide in hepatocellular carcinoma patients' plasma. A proper analytes' separation was obtained with Synergi Fusion RP column (4 µm, 80 Å, 50 × 2.0 mm) using a gradient elution of 10 mM ammonium acetate with 0.1% formic acid (mobile phase A) and methanol:isopropanol (90:10, v/v, mobile phase B) containing 0.1% formic acid. The analysis was then performed by electrospray ionization in negative mode coupled with a triple quadrupole mass spectrometry, API 4000QT, monitoring two transitions for each analyte, one for the quantification and the other for confirmation. The method could be easily applied to the clinical practice thanks to the short run (7 min), the low amount of patient plasma necessary for the analysis (5 µL) and the fast sample processing based on protein precipitation. The method was therefore fully validated according to FDA and EMA guidelines. The linearity was assessed (R2≥0.998) over the concentration ranges of 50-8000 ng/mL for SORA and REGO, and 30-4000 ng/mL for their metabolites, that appropriately cover the therapeutic plasma concentrations. The presented method also showed adequate results in terms of intra- and inter-day accuracy and precision (CV ≤ 7.2% and accuracy between 89.4% and 108.8%), recovery (≥85.5%), sensitivity, analytes stability under various conditions and the absence of the matrix effect. Once the validation was successfully completed, the method was applied to perform the Cmin quantification of SORA, REGO and their metabolites in 54 plasma samples collected from patients enrolled in a clinical study ongoing at the National Cancer Institute of Aviano.