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.