PEGylation was found to be a promising approach to improve the anti-myocardial ischemic activity of Radix Ophiopogonis polysaccharide (ROP) by prolonging its retention in plasma. To fully evaluate the effectiveness and safety of this strategy, the tissue distribution of PEGylated ROP was investigated in this study. A long-circulating and bioactive PEGylated ROP with 1.04 mol 20-kDa mPEG per mol ROP ((1.04)P(20k)-R) was prepared by a moderate coupling reaction between the hydroxyl-activated ROP and the amino-terminated mPEG. Its tissue distribution in mice with normal and ischemic myocardium was studied and compared with ROP. The results show that the descending order of tissue distribution of 1.04P20k-R ranked by AUC was kidney, lung, heart, liver, and brain in normal mice and kidney approximate to lung approximate to heart, liver and brain in mice with myocardial ischemia. With the exception of the heart, myocardial ischemia did not cause obvious changes in the distribution of (1.04)P(20k)-R in the other tissues studied. Owing to the enhanced permeability and retention effect caused by ischemia, the AUC of (1.04)P(20k)-R in ischemic hearts was approximately 1.6-fold greater than in normal hearts. Compared with ROP in rats, the distribution tendency of (1.04)P(20k)-R in mouse kidney, brain, and lung was reduced by approximately 42, 1.6, and 1.3 times, respectively, whereas it was increased by approximately 1.3-fold in the liver. The results of this study are highly instructive for the further pharmaceutical development of PEGylated ROP. (C) 2011 Elsevier B.V. All rights reserved.
[1]Shanghai Univ Tradit Chinese Med, Engn Res Ctr Modern Preparat Technol TCM, Minist Educ, Shanghai 201203, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, Coll Chinese Mat Med, Shanghai 201203, Peoples R China.
[3]Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Shanghai 201203, Peoples R China.
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