ABSTRACT
Objective To investigate the effect of lipid encapsulated 1,1,2-trichlorotrifluoroethane phase change nanodroplets for high intensity focused ultrasound (HIFU) ablation.Methods The lipid encapsulated 1,1,2-trichlorotrifluoroethane phase change nanodroplets was prepared with membrane hydration method,and its physicochemical properties were examined.The synergistic effect of HIFU ablation was verified with experiments in vitro and in vivo experiments.For in vitro experiment,the isolated bovine liver tissues were irradiated with HIFU (250 W,10 s,continuous wave).For in vivo experiment,the livers of New Zealand rabbits were irradiated with HIFU (200 W,5 s,continuous wave).The volume of coagulative necrosis,energy efficiency factors (EEF) and the volume of the hyperechoic area after HIFU radiation were measured.And the statistical analysis was performed.Results Phase change nanoparticles were spherical in solution and uniform in size.For in vitro experiment,the coagulative necrosis volume,EEF and hyperechoic area of bovine liver tissue injected with nanodroplets were significantly higher than those of untreated bovine liver tissue (t=28.80,19.55,14.30;P=0.01,0.02,0.02) after HIFU.For in vivo experiment,the coagulative necrosis volume,EEF and hyperechoic area of rabbit liver tissue injected with nanodroplets were significantly higher than those of untreated rabbit liver tissue (t=9.41,13.52,15.67;P=0.02,0.01,0.01) after HIFU.Conclusion The lipid encapsulated 1,1,2-trichlorotrifluoroethane phase change nanodroplets can significantly improve the efficiency of HIFU ablation significantly.
ABSTRACT
Aims: A novel nanocarrier was formulated by remote loading of doxorubicin (Dox) into a dipalmitoylphosphatidylcholine (DPPC) liposome that also contains various perfluorocarbon (PFC) droplets within its aqueous interior. It was shown that Dox can be loaded to a level of up to 67% into these large unilamellar vesicles composed of DPPC and cholesterol by employing a transmembrane pH gradient technique. Methods: The different encapsulation efficiencies for these eLipoDox constructs of differing PFC composition are 45.5% (PFC5), 31.5% (PFC6) and 66.7% (PFC5/PFC6 mixture, PFCm). At 30 seconds of insonation, the eLipoDox formulation with PFCm droplets appeared to release more Dox than did eLipoDox with pure PFC5 or PFC6 droplets. The thermal stability of these eLipoDox formulations were examined at 37°C at different times; then controlled delivery was demonstrated by applying low-frequency ultrasound (US) at 1 W/cm2. Results: The eLipoDox with PFC6 or PFCm showed the best combination of thermal stability and drug release. An immunoblotting analysis indicates that ultrasound-triggered Dox release from eLipoDox could provide a higher quantity of nanodrug into tumor cells and thus may have cytostatic effects in cancer cells. Conclusion: These eLipoDox constructs with low boiling point PFCs have the potential to provide more effective ultrasonically activated drug therapy to a desired location.