(164g) Temperature Response of Poly (L-lactide-co-ethylene glycol) Stabilized Perfluoropentane Micro-Droplets

Bubbles have been extensively used as a contrast agent for ultrasound imaging. Gramiak and Shah reported first small gas bubbles for use in contrast enhanced ultrasound, and the air bubbles were replaced by non-soluble gases like perfluorocarbons [1]. A stabilizing shell with lipids or surfactants has been used to increase the stability of these microbubbles in a system. The acoustic vaporization of PFP droplets has been studied previously [2], but temperature effects on formation and growth of bubbles from droplet emulsion have not been extensively studied. Embolization has been a popular alternative for hepatocellular carcinoma as well as brain tumor patients, where arteries feeding the tumors are blocked so that the tumors can be excised without excessive bleeding [3-5]. Our goal is to use stable microdroplets to cause occlusion similar to embolization. An external trigger such as a temperature increase will induce formation of microbubbles and coalescence of microbubbles from the emulsion of microdroplets; and eventually leading to occlusion. We would like to report the response of surfactant stabilized perfluoropentane (PFP) emulsions to elevated temperatures. Block polymer of poly (L-lactide-co-ethylene glycol) of varying concentrations was used as the stabilizing agent to form PFP droplets. The molecular weight of the block copolymers are 5000 Da and 4700 Da for PEG and PLLA respectively. We characterized the size distribution of micelles and droplets in surfactant and emulsion solutions respectively, by dynamic light scattering (DLS). We observed micellar and lamellar structures of surfactant using transmission electron microscope (TEM). We investigated the surfactant properties and the surfactant-PFP interfacial properties using measurements of viscosities of both surfactant and emulsion solutions as a function of temperature, and measurements of interfacial energies between PFP and surfactant. We observed the formation and growth of microbubbles in the emulsion filled microchannel that was subjected to elevated temperatures of up to 45 °C (Figure 1a). We calculated the change in number and volume of bubbles as a function of temperature and concentration (Figure 1b). The growth and formation of the bubbles were attributed to change in surfactant structure at higher temperatures, leading to increase in coalescence of droplets to the bubbles and diffusion of dissolved gases from the solution into the bubble. Using infrared imaging, we observed phase transition of PFP droplets to vapor at the interface of bubbles formed in the microchannel as indicated by cold spots in figure 1c. Low surfactant concentration leads to larger bubbles due to decreased stability of the surfactant covered microdroplets. We would like to discuss the surface tension and viscosity results; combined with the understanding of stability of surfactants with temperature to explain the formation and growth of microbubbles from the surfactant stabilized PFP emulsion, at higher temperatures. REFERENCES 1. Gramiak, R. and P.M. Shah, Echocardiography of the aortic root. Invest Radiol, 1968. 3(5): p. 356-66. 2. Kripfgans, O.D., et al., On the acoustic vaporization of micrometer-sized droplets. J Acoust Soc Am, 2004. 116(1): p. 272-81. 3. Ishida, N., et al., Complete necrosis of a giant tumor in liver by transcatheter arterial embolization and percutaneous transhepatic portal embolization before liver resection. Nippon Shokakibyo Gakkai Zasshi, 2008. 105(8): p. 1226-33. 4. Liu, W.G., et al., Effect of preoperative transcatheter arterial chemo-embolization on activity of cell proliferation in Wilms tumor. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2008. 37(1): p. 83-7. 5. Shibata, T., et al., Transcatheter arterial embolization for tumor seeding in the chest wall after radiofrequency ablation for hepatocellular carcinoma. Cardiovasc Intervent Radiol, 2006. 29(3): p. 479-81.