Multiple-Exposure Drug Release from Stable Nanodroplets by High-Intensity Focused Ultrasound for a Potential Degenerative Disc Disease Treatment

Abstract

The combination of simvastatin and CF680 dye encapsulated by stable nanodroplets has been developed as a drug delivery carrier. Simvastatin has previously been found to be a potential degenerative disc disease treatment. Multiple exposures of the nanodroplets to high-intensity focused ultrasound induced release of simvastatin. Each ultrasound exposure yielded a consistent concentration of the drug and dye released. B-mode ultrasound image analysis data and cavitation data clearly indicated the release mechanism is phase transition of the liquid nanodroplets into gas bubbles. The nanodroplets were stably stored in ex vivo rabbit spinal discs for at least 14 days, and the contents responded to ultrasound exposure on demand. Lastly, nucleus pulposus cells harvested from rabbit spine discs and exposed to media with nanodroplets exhibited a decrease in cell viability (85%) relative to the cells only (96.7%) at 24 h, but no difference at 48 h. Thus, the system may be a potential degenerative disc disease treatment.

Keywords: Degenerative disc disease; High-intensity focused ultrasound; Multiple releases; On-demand drug release.