The Effect of Lipid Solubilization on the Performance of Doxorubicin-Loaded Nanobubbles

Microbubbles (MBs) have been recently studied as a drug-carrier for cancer theranostics. However, their effectiveness in vivo is limited by their large size (1-8 um). Drug-loaded nanobubbles (NBs), with a footprint of 100-600 nm, can facilitate extravasation, resulting in higher drug accumulation in tumors and improved efficacy. In this study, we report on the effect of lipid solubilization on drug loading and acoustic performance of doxorubicin-loaded NBs. Specifically, we evaluated the effects of a membrane additive, glycerol, and a pre-solubilizing agent, propylene glycol on the NBs. The results showed that the lipid solubilization method used affected the size, concentration and stability of the drug-loaded contrast agent. The addition of glycerol had negligible effect on initial echogenicity but affected the long-term stability of the bubble. Propylene glycol affected the initial echogenicity and loading efficiency of bubbles. Overall, this investigation shows that the shell composition and preparation methods used for lipid solubilization could influence the ultrasound response of NBs as well as the efficiency of incorporating drug into the bubbles. Both of these parameters can greatly impact the research and development of NBs for use as a theranostic agent.