In vivo biological evaluation of high molecular weight hyperbranched polyglycerols

被引:187
作者
Kainthan, Rajesh K.
Brooks, Donald E.
机构
[1] Univ British Columbia, Dept Pathol & Lab Med, Ctr Blood Res, Vancouver, BC V6T 2B5, Canada
[2] Univ British Columbia, Dept Chem, Vancouver, BC V6T 2B5, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会; 加拿大创新基金会;
关键词
hyperbranched polyglycerol; animal toxicity; biocompatibility; drug delivery; biodistribution; pharmacokinetics;
D O I
10.1016/j.biomaterials.2007.07.046
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Hyperbranched polyglycerols (HPGs) are water-soluble polyether polyols that can be synthesized in a controlled manner with low polydispersity. Recently we reported the synthesis and characterization of very high molecular weight and narrowly polydispersed HPGs that could be used as potential alternatives to high generation dendrimers, their advantage being the relative simplicity of synthesis. Reported in this article are the pharmacokinetic properties of these polymers. Two polymers of number average molecular weights 106,000 and 540,000 were tested in mice for their pharmacokinetic behavior. The plasma half-life for the lower molecular weight polymer was around 32 h whereas that of the higher molecular weight HPG was similar to 57 h. Our results show that these high molecular weight HPGs, which can be prepared in a single step reaction, are potential candidates for drug delivery and imaging applications where a long circulating polymer is highly desirable. A detailed tissue distribution profile of these polymers as a function of molecular weight is described. These polymers were also found to be hydrolytically stable and the concentration dependence of solution viscosity measurements suggested the absence of any aggregation. (c) 2007 Published by Elsevier Ltd.
引用
收藏
页码:4779 / 4787
页数:9
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