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Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats

Authors Yao CX, Shi XL, Lin X, Shen L, Xu DS, Feng Y

Received 30 August 2014

Accepted for publication 16 October 2014

Published 9 January 2015 Volume 2015:10(1) Pages 409—418

DOI https://doi.org/10.2147/IJN.S73462

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster

ChunXia Yao,1,2,* XiaoLi Shi,1,* Xiao Lin,1,2 Lan Shen,1 DeSheng Xu,3 Yi Feng2

1College of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China

*These authors contributed equally to this work as co-first authors


Abstract: Although PEGylation plays an important role in drug delivery, knowledge about the distribution behavior of PEGylated drugs in ischemic myocardia is rather limited compared to nanoparticles. This work therefore aims to characterize the targeting behavior of the anti-myocardial ischemic mono-PEGylated conjugates of Radix Ophiopogonis polysaccharide (ROP) in two clinically relevant animal models, ie, the myocardial infarction (MI) model and the ischemia/reperfusion (IR) model. To determine the effect of the molecular size of conjugates, two representative conjugates (20- and 40-kDa polyethylene glycol mono-modified ROPs), with hydrodynamic size being approximately and somewhat beyond 10 nm, respectively, were studied in parallel at three time points postdose after a method for determining them quantitatively in biosamples was established. The results showed that the cardiac distribution of the two conjugates was significantly enhanced in both MI and IR rats due to the enhanced permeability and retention effect induced by ischemia. In general, the cardiac targeting efficacy of the conjugates in MI and IR rats was approximately 2; however, different changing in targeting efficacy with time was observed between MI and IR rats and also between the conjugates. Although the enhanced permeability and retention effect-based targeting efficacy for mono-PEGylated ROPs was not high, they, as dissolved macromolecules, are prone to diffusion in the cardiac interstitium space, and thus, facilitate the drug to reach perfusion-deficient and nonperfused areas. These findings are helpful in choosing the cardiac targeting strategy.

Keywords: heart distribution, myocardial ischemia, polyethylene glycol, Radix Ophiopogonis polysaccharide

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