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BIOBOARD
Nanoparticle Combination Drug Delivery Therapy for Atherosclerosis
Researchers from The Korea Advanced Institute of Science and Technology (KAIST) designed physiochemical cargo-switching nanoparticles (CSNP) to help significantly reduce cholesterol and macrophage foam cells in arteries.

Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of cholesterol and cholesterol-loaded macrophage foam cells in the tunica intima of the arteries. The formation of the atherosclerotic plaque will cause the narrowing of artery walls, restricting blood flow and cause various cardiovascular conditions such as heart attacks and strokes.

In this study, the CSNP-based combination drug delivery therapy proved to exert cholesterol-lowering, anti-inflammatory, and anti-proliferative functions. This method matched the functions of two common medications for treating and preventing atherosclerosis; cyclodextrin and statin. Professor Ji-Ho Park and Dr. Heegon Kim from KAIST's Department of Bio and Brain Engineering said their study has shown great potential for future applications with reduced side effects.

Despite oral statin being the clinical standard care for atherosclerosis, it has shown only modest efficacy in eliminating an established plaque. Which results in patients having to take statin drugs for the rest of their lives and will always carry the risk of plaque ruptures that can trigger a blood clot.

To address these issues, Professor Park and Dr. Kim exploited another antiatherogenic agent called cyclodextrin. In their paper published in the Journal of Controlled Release on 10 March 2020, Professor Park and Dr. Kim reported that the polymeric formulation of cyclodextrin with a diameter of approximately 10 nm can accumulate within the atherosclerotic plaque 14 times more and effectively reduce the plaque even at lower doses, compared to cyclodextrin in a non-polymer structure.

Although cyclodextrin is known to have a cytotoxic effect on hair cells in the cochlea, which can lead to hearing loss, cyclodextrin polymers developed by Professor Park's research group exhibited a varying biodistribution profile and did not have this side effect.

In the follow-up study reported in ACS Nano on 28 April 2020, the researchers exploited both cyclodextrin and statin to form the cyclodextrin-statin self-assembly drug complex. The complex formation processes were optimized to obtain consistent and stable nanoparticles with a diameter of about 100 nm for systematic injection.

The therapeutic synergy of cyclodextrin and statin could reportedly enhance plaque-targeted drug delivery and anti-inflammation. Cyclodextrin led to the regression of cholesterol in the established plaque, and the statins were shown to inhibit the proliferation of macrophage foam cells. The study suggested that combination therapy is required to resolve the complex inflammatory cholesterol-rich microenvironment within the plaque.

Professor Park said, "While nanomedicine has been mainly developed for the treatment of cancers, our studies show that nanomedicine can also play a significant role in treating and preventing atherosclerosis, which causes various cardiovascular diseases that are the leading causes of death worldwide."

 

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