Spherical nanoparticles as a classic delivery vehicle for anticancer drugs have been extensively investigated, but study on the shape of nanoparticles has received little attention until now. Here, a nonspherical poly(ethylene glycol) (PEG)-stabilized bilayer nanodisk consisting of 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC) and PEG5000-glyceryl distearate (PEG5K-GCDS) was prepared for doxorubicin delivery, called DOX-Disks. The prepared disks were open bilayer structures, with a hydrophobic discoid center built by DSPC and a hydrophilic PEG edge. Mean particle diameter of the disk was 80.14 nm, and the disk height was about 6 nm with aspect ratio about 12. Encapsulation efficiency of DOX-Disks was as high as 96.1%, and DOX release from DOX-Disks was pH-dependent (25.6% of total DOX released at 24 h in pH 7.4). The pharmacokinetic performances showed that DOX-Disks demonstrated long circulation time in blood and larger AUC (11.7-fold of t1/2 and 31.7-fold of AUC) in rats compared with DOX solutions (DOX-Sol). Tissue distribution in H22 tumor bearing mice demonstrated higher tumor accumulation (9.7-fold) and lower heart toxicities (25.7-fold) at 48 h after iv administration, in comparison with DOX-Sol. In addition, DOX-Disks exhibited much effectiveness in inhibiting tumor cell growth, and the IC50 values were 2.03, 0.85, and 0.86 μg/mL for DOX-Sol and 0.23, 0.24, and 0.20 μg/mL for DOX-Disks after treatment for 48, 72, and 96 h against MCF-7/Adr cells, respectively. DOX-Disks were taken up into MCF-7/Adr cells via energy-dependent endocytosis processes, involved in clathrin-mediated, macropinocytosis-mediated, and non-clathrin- and non-caveolae-mediated endocytosis pathways. In summary, such PEG-stabilized bilayer nanodisks could be one of the promising carriers for antitumor drugs via extended blood circulation and improved tumor distribution.
The present study was designed to systematically investigate the chemical profile differences between crude Anemarrhenae rhizoma (CAR) and salt-processed Anemarrhenae rhizoma (SAR). Ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–QTOF-MS), coupled with multivariate statistical analysis was used for the discrimination of chemical profiles and the identification of the differentiation of the chemical constitutions of CAR and SAR. In addition, seven main constituents of CAR and SAR were simultaneously determined by ultra-high-performance liquid chromatography–quadrupole mass spectrometry (UHPLC–MS) for analyzing the content variations. A total of 24 components were found to be the main contributors to the significant difference between CAR and SAR. The structures of the marker compounds were identified based on their chromatographic behaviors, intact precursor ions, and characteristic MS fragmentation patterns. The potential structural transformation mechanism of furostanol saponins during salt processing was explored. The results may provide a scientific foundation for deeply elucidating the processing mechanism of Anemarrhenae rhizoma.
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