Abstract
Xenon is a cellular protectant shown to stabilize or reduce neurologic injury in stroke. The goal of this work was to develop lipid-shelled microbubbles for ultrasound-triggered xenon release. Microbubbles loaded with either xenon alone (Xe-MB) or xenon and octafluoropropane (Xe-OFP-MB) were synthesized by high-shear mixing lipids with either 100% xenon, or 90% (v/v) xenon and 10% (v/v) octafluoropropane. The size distribution and the attenuation coefficient of Xe-MB and Xe-OFP-MB were measured using a Coulter counter and a broadband attenuation spectroscopy system, respectively. Gas chromatography/mass spectrometry (GC/MS) was performed to assess the dose and stability of encapsulated xenon. The feasibility of xenon release using 5-MHz pulsed Doppler ultrasound and 220-kHz pulsed ultrasound was tested by ultrasound attenuation spectroscopy. Co-encapsulation of OFP increased the number density, attenuation coefficient, and temporal stability of microbubbles. The GC/MS measurements revealed that 143 ± 20 μL/mg and 131 ± 33 μL/mg of xenon was loaded in Xe-MB and Xe-OFP-MB, respectively. Xe-MB and Xe-OFP-MB retained 54 ± 11% and 66 ± 1% of the xenon payload within 15 min of activation, respectively. Attenuation measurements confirmed ultrasound-triggered xenon release. These results suggest that lipid-shelled microbubbles with OFP could serve as ultrasound-triggered xenon delivery agents to attenuate cellular breakdown.
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