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

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

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...

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Autores principales: Yao CX, Shi XL, Lin X, Shen L, Xu DS, Feng Y
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/d59f12faad894cf8addbf3509ec90f3b
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spelling oai:doaj.org-article:d59f12faad894cf8addbf3509ec90f3b2021-12-02T03:11:45ZIncreased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats1178-2013https://doaj.org/article/d59f12faad894cf8addbf3509ec90f3b2015-01-01T00:00:00Zhttp://www.dovepress.com/increased-cardiac-distribution-of-mono-pegylated-radix-ophiopogonis-po-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 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 polysaccharideYao CXShi XLLin XShen LXu DSFeng YDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 409-418 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Yao CX
Shi XL
Lin X
Shen L
Xu DS
Feng Y
Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats
description 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
format article
author Yao CX
Shi XL
Lin X
Shen L
Xu DS
Feng Y
author_facet Yao CX
Shi XL
Lin X
Shen L
Xu DS
Feng Y
author_sort Yao CX
title Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats
title_short Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats
title_full Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats
title_fullStr Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats
title_full_unstemmed Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats
title_sort increased cardiac distribution of mono-pegylated radix ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/d59f12faad894cf8addbf3509ec90f3b
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