Investigating the Release Mechanism of Calcein from eLiposomes at Higher Temperatures

Numerous nanocarriers are currently being investigated as drug delivery vehicles for transporting chemotherapeutics to cancer cells. Our research group has recently synthesized a new generation of echogenic liposomes based on the concept of encapsulating one or more nanoemulsion droplets inside a liposome (called an eLiposome). The concept is to use a nanoemulsion droplet with a low boiling point near body temperature, thus requiring only a small acoustic nudge to vaporize the droplet from liquid to gas and break open the eLiposome, thus releasing its contents. The purpose of this note is twofold. First, we wanted to show experimentally that eLiposomes remained stable at body temperature and retained their potential to deliver drugs through the ultrasonically-activated expansion of the emulsion nanodroplet. Additionally, we examined the physical mechanism potentially involved in the release of calcein at higher temperatures. Experimental results using calcein as a model drug confirmed the eLiposome stability at physiological temperatures and suggested that heterogeneous nucleation theory was capable of capturing the general release characteristics observed in this study. Heterogeneous nucleation of gas is possibly the main mechanism at play in passive release from eLiposomes at temperatures above body temperature. More research is needed to confirm the definitive physics of the model drug's release from these novel nanovehicles.