title: Mono-PEGylated radix ophiopogonis polysaccharide for the treatment of myocardial ischemia.
abstract: This work aimed to improve the clinical application of Radix Ophiopogonis polysaccharide (ROP), a natural anti-myocardial ischemic fructan with Mw of 4.80 kDa, by mono-PEGylation. Three mono-PEGylated ROPs were prepared by a moderate coupling reaction between amino-terminated methoxy-PEG (20-, 30-, or 40-kDa) and excessive hydroxyl-activated ROP. After being fully characterized by proton nuclear magnetic resonance as well as high-performance gel permeation chromatography and anthrone-sulfuric acid colorimetry coupled assay, they were evaluated for pharmacokinetics and anti-myocardial ischemic activities in rats with coronary artery ligation. The results showed that mono-PEGylated ROPs were successfully and effectively prepared. Compared with ROP, the three mono-PEGylated ROPs showed approximately 32-, 85-, and 100-fold prolonged retention in systemic circulation with plasma half-lives reaching 16.1, 42.4, and 49.8 h, respectively. Studies on anti-myocardial ischemic effects of the conjugates showed that administrated at the same molar dose of 4 μ mol/kg per injection as ROP, they could achieve comparable or even better therapeutic effects although their administration intervals were 2- to 6-fold longer than that of ROP. These findings confirm that PEGylation would be a promising approach to markedly reducing the injection-administered frequency of ROP and hence patient compliance without sacrifice of the therapeutic efficacy by significantly improving its pharmacokinetics.
authors.affiliation: College of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
authors.forename: GuiLan
authors.initials: G
authors.lastname: Sun
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.forename: Lan
authors.initials: L
authors.lastname: Shen
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.forename: DeSheng
authors.initials: D
authors.lastname: Xu
authors.forename: KeFeng
authors.initials: K
authors.lastname: Ruan
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D019668:Liliaceae; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008517:Phytotherapy; D028321:Plant Preparations; D018517:Plant Roots; D011092:Polyethylene Glycols / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D002316:Cardiotonic Agents; D028321:Plant Preparations; D011134:Polysaccharides; D011092:Polyethylene Glycols; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase
keywords: Characterization; Myocardial ischemia; Polyethylene glycol; Polysaccharide; Radix Ophiopogonis