In atherosclerosis, damaged endothelial cells (EC) overproduce reactive oxygen species (ROS) and generate inflammatory mediators, which recruit monocytes to the EC.  As scavengers of ROS, antioxidants hold great promise to alleviate the symptoms of cardiovascular diseases and atherosclerosis.  Therefore, antioxidants are good therapeutic drug candidates; however, antioxidant enzymes such as catalase are easily degraded by proteases in vivo and chemical mimetics of superoxide dismutase such as tempol and tempo require a target-specific delivery system since hydrophobic tempol or tempo are nonspecific and can diffuse into any type of cells.  Here, we report a novel monocyte-based drug delivery system encapsulating either catalase or tempol/tempo.  The monocyte as a novel drug delivery vehicle offers advantages over other delivery systems due to its target specificity to damaged EC.  The delivery system can also be easily fabricated in biological conditions and keeps antioxidants active.  In this research, membrane impermeable catalase with protease inhibitors was formulated in monocytes via a hypotonic/resealing method and membrane permeable tempol/tempo were encapsulated in monocytes via passive diffusion.  Target specificity and enhanced activities of antioxidants scavenging ROS have been demonstrated by in vitro study.  We anticipate numerous applications of the monocyte-based drug delivery system, given its target specificity to activated EC.

Monocyte-based drug delivery system targeting atherosclerosis

247th National Meeting (2014)

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