Preparation and Propeties of Third-Generation Taxoid Loaded Targeted Delivery Micelles

Third-generation taxoid contains difluorovinyl (DFV) in its structure, which significantly reduces the binding ability of P-glycoprotein (P-gp) with the drug molecules, thereby reducing drug efflux from tumor cells. Compared to the marketed first- and second-generation taxoids (paclitaxel, docetaxel, and cabazitaxel), third-generation taxoid has better resistance to multidrug resistance and more significant tumor inhibition efficacy. To achieve targeted drug delivery of third-generation taxoid in tumor cells, an amphiphilic block copolymer capped with lipoic acid was synthesized and reduction-sensitive polymeric micelles encapsulating third-generation taxoid (SB5706) were prepared using solid dispersion-thin film hydration method. The encapsulation of the drug was characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance hydrogen spectroscopy (¹H-NMR). Drug loading capacity and encapsulation rate of the micelles were determined by ultraviolet spectroscopy (UV). The stability of the drug loaded micelles in vitro was examined, and the in vitro release pattern and in vivo tumor suppression effect were studied. The results showed that the micelles had homogeneous particle size, good stability and reduction-sensitive controlled drug release characteristics, and the inhibitory effect of the micelles on A549 lung adenocarcinoma was significantly stronger than that of the commercial available formulation nab-paclitaxel.