Enhanced release of anticancer agents from nanoliposomes in response to diagnostic ultrasound energy levels

The efficacy of diagnostic ultrasound is explored for the release of anticancer agents loaded inside liposomes. Diagnostic ultrasound energy levels employed in the study were at a frequency of 7.5MHz and the highest power intensity which is a function of the pulse repetition time. Design of Experiments was used to formulate the Ultrasound sensitive nanoliposome (USNL) by varying the lipid ratios and the intensity settings of ultrasound energy. Doxorubicin was loaded into the USNL and the release was compared to conventional Doxil liposomes. The USNLs released increasing amounts of drug in response to increasing irradiation times while the drug release was not significant when the Non-USNLs (Doxil liposomes) were exposed to ultrasound energy levels. In vitro studies to test the cytotoxicity of the formulations showed that the USNLs significantly inhibited cell survival of SCC9, squamous oral cancer cells, as compared to the Non-USNLs. We hypothesize that the drug is released due to increased membrane permeability during exposure to ultrasound energy levels, where the lipid composition and energy levels play a key role in determining the efficacy of diagnostic ultrasound energy as a tool for drug delivery.