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Polymeric Micelles as Pharmaceutical Carriers
Published in Ijeoma F. Uchegbu, Andreas G. Schätzlein, Polymers in Drug Delivery, 2006
An interesting new approach is the intracellular delivery of micelles. As PEG-PE micelles have been found to carry a net negative charge [111], which might hinder their internalization by cells, the alteration of this negative charge by the addition of positively charged lipids to PEG-PE was suggested in order to improve the endocytic uptake of micelles by cancer cells, thus increasing the efficiency of this drug delivery system [109]. Moreover, after endocytosis, drug- or DNA-loaded particles are able to escape from the endosomes and enter the cytoplasm of most cells because of the interaction between cationic lipids and the endosomal membranes [139]. Therefore, it is possible that after enhanced endocytosis, paclitaxel-loaded PEG-PE: positively charged lipid mixed micelles could escape from endosomes and enter the cytoplasm of cancer cells, where paclitaxel could be slowly released from the micelles and kill cancer cells with a higher efficiency than the free drug or drugs in negatively charged PEG-PE micelles. The addition of positively charged lipids facilitated the intracellular uptake and cytoplasmic delivery of paclitaxel-containing micelles as evidenced by the fact that the anticancer effect of paclitaxel in mixed (positively-charged-lipid-containing) micelles was significantly greater than that of free paclitaxel and of paclitaxel in PEG-PE micelles in two cancer cell lines. In A2780 cancer cells, the IC50 values of free paclitaxel, paclitaxel in PEG-PE micelles, and paclitaxel in PEG-PE: positively charged lipid mixed micelles were 12.2, 3.9, and 0.7 µM, respectively. Similar results were also obtained with BT-20 cancer cells. The endosome-destabilizing effect and cytoplasmic delivery of drug-loaded mixed micelles were also confirmed by fluorescence microscopy. Similarly, PEG-PE-based micelles loaded with the anticancer vitamin K3 and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) were more cytotoxic than micelles with only vitamin K3, because DBU facilitated endosomal destabilization and cytoplasmic delivery of vitamin K3 [140].
Synthesis, X-ray structures, and biological activity of Zn(II) and cd(II) complexes with pyridine thiazolone derivatives
Published in Journal of Coordination Chemistry, 2021
Xunzhong Zou, Yanzhi Liao, Chaojie Yang, Ansheng Feng, Xiaoyun Xu, Huifeng Jiang, Yu Li
Evaluation of the cytotoxic activity of the ligands and their metal complexes were carried out in vitro using the MTT assay [19,20]. The compounds, alongside cisplatin, were dispersed in PEG400, diluted with water to the gradient concentrations (0, 5, 10, 20, 40, 80, and 160 μg/mL) and subjected to cell line tests towards human lung cancer cells (A549), human breast cancer cells (BT-20), human ovarian cancer cells (MCF-7), and human osteosarcoma cells (U20S). About ten million cells were seeded in 96-well plates for 24 h and then treated with different concentrations of samples at 37 °C with 5% CO2 for 48 h thereafter. Cells were then fixed, washed, and exposed to MTT reagent for 4 h to form MTT formazan dye, which was measured at 570 nm, with 690 nm as a reference interval using the Microplate Reader.