John Garner

PEG-PLGA from PolySciTech used in research on PEGylated long-circulating nanoparticles

Blog Post created by John Garner on Aug 20, 2018

Zhuo, 2018 dense PEG polyscitech.jpg

One of the mechanisms for loss of nanoparticles from the blood-stream is removal by macrophages. This process is particularly pronounced in the liver, where particles are up-taken as part of hepatic clearance of ‘non-self’ components from the blood-stream. One means of preventing macrophage uptake is the addition of a pegylated shell to the outside of the nanoparticle as PEG reduces non-specific protein adsorption. Recently, researchers at Drexel University utilized mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to generate PEGylated nanoparticles and tested the particles under a variety of conditions to obtain a better understanding of how these particles can be modified to prevent clearance from the blood-stream. This research holds promise for the development of improved long-circulating nanoparticle drug-delivery systems. Read more: Zhou, Hao, Zhiyuan Fan, Peter Y. Li, Junjie Deng, Dimitrios C. Arhontoulis, Christopher Y. Li, Wilbur B. Bowne, and Hao Cheng. "Dense and Dynamic Polyethylene Glycol Shells Cloak Nanoparticles from Uptake by Liver Endothelial Cells for Long Blood Circulation." ACS nano (2018). https://pubs.acs.org/doi/abs/10.1021/acsnano.8b04947

 

“Research into long-circulating nanoparticles has in the past focused on reducing their clearance by macrophages. By engineering a hierarchical polyethylene glycol (PEG) structure on nanoparticle surfaces, we revealed an alternative mechanism to enhance nanoparticle blood circulation. The conjugation of a second PEG layer at a density close to, but lower than the mushroom-to-brush transition regime on conventional PEGylated nanoparticles dramatically prolongs their blood circulation via reduced nanoparticle uptake by non-Kupffer cells in the liver, especially liver sinusoidal endothelial cells (LSECs). Our study also disclosed that the dynamic outer PEG layer reduces protein binding affinity to nanoparticles, although not the total number of adsorbed proteins. These effects of the outer PEG layer diminishes in the higher density regime. Therefore, our results suggest that the dynamic topographical structure of nanoparticles is an important factor in governing their fate in vivo. Taken together, this study advances our understanding of nanoparticle blood circulation and provides a facile approach for generating long circulating nanoparticles.”

 

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