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Published on: January 28, 2021
Targeted delivery of atorvastatin via asialoglycoprotein receptor (ASGPR)
Youxi Zhang1, Xinfu Zhang2, Chunxi Zeng3
1Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States; Department of Pharmacy, The Fourth Affiliated Hospital of China Medical University, No. 4, Chongshan Eastern Road, Shenyang 110032, China.
Abstract:
Targeted drug delivery platforms can increase the concentration of drugs in specific cell populations, reduce adverse effects, and hence improve the therapeutic effect of drugs. Herein, we designed two conjugates by installing the targeting ligand GalNAc (N-acetylgalactosamine) onto atorvastatin (AT). Compared to the parent drug, these two conjugates, termed G2-AT and G2-K-AT, showed increased hepatic cellular uptake. Moreover, both conjugates were able to release atorvastatin, and consequently showed dramatic inhibition of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) reductase and increased LDL receptors on cell surface.
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