Coalescence of drug-carrier microbubbles*

Microbubbles can be used for targeted therapy. This novel application requires enhancing their response to ultrasound waves. Bubbles with the same composition will have the same response to the ultrasound if they have monodisperse size distribution. The fabrication of monodisperse microbubbles is achieved using microfluidic devices. However, these bubbles can be difficult to collect and usually have short lifespans. Segers et al. [Lab chip 19, 158-167 (2019)] recently constructed a model describing the coalescence probability of bubbles with only-lipid membranes produced in flow-focusing devices. They proved that temperature, lipid concentration, and the amount of pegylated lipids alter the coalescence probability. In this work, we study the coalescence of bubbles when drug molecules are added to their membrane.

We used doxorubicin (DOX), a first-line drug used for chemotherapy, to evaluate its effect on coalescence probability. The lipid bubble membranes were made of DPPC: DPPS: DPPE-PEG5000. We added DOX to the lipid mixture at different concentrations to evaluate the drug impact. The bubbles were produced by using a flow-focusing device. In the device, the liquid phase (lipid solution) and the gaseous phase (pure nitrogen) flow through a small constriction where the gas thread is disrupted, and the bubbles are pinched off and flow upstream to the outlet. We obtain the coalescence probability and relative viscosity curves as a function of drug concentration.