In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.
Purpose The transpiration has been recognized as one of the most effective thermal protection methods for future hypersonic vehicles. To improve efficiency and safety, it is urgent to optimize the design of the transpiration system for heat and drag reduction. The purpose of this paper is to investigate the effects of transpiration on heat and drag reduction. Design/methodology/approach A chemical nonequilibrium flow model with the transpiration is established by using Navier–Stokes equations, the shear-stress transport turbulence model, thermodynamic properties and the Gupta chemical kinetics model. The solver programmed for this model is verified by comparing with experimental results in the literature. Effects of air injection on the flow field, the aerodynamic resistance and the surface heat flux are calculated with the hypersonic flow past a blunt body. Furthermore, a modified blocking coefficient formula is proposed. Findings Numerical results show that the transpiration can reduce the aerodynamic resistance and the surface heat flux observably and increase the shock wave standoff distance slightly. It is also manifested that the modified formula is in better agreement with the wind tunnel test results than the original formula. Originality/value The modified formula can expand the application range of the engineering method for the blocking coefficient. This study will be beneficial to carry out the optimal design of the transpiration system.
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