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用于药物递送应用的细胞外基质结合混合胶束

Extracellular matrix binding mixed micelles for drug delivery applications.

作者信息

O'Neil Conlin P, van der Vlies André J, Velluto Diana, Wandrey Christine, Demurtas Davide, Dubochet Jacques, Hubbell Jeffrey A

机构信息

Institute for Bioengineering and Institute for Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 15, CH-1015 Lausanne, Switzerland.

出版信息

J Control Release. 2009 Jul 20;137(2):146-51. doi: 10.1016/j.jconrel.2009.03.013. Epub 2009 Mar 27.

Abstract

We present the formation of collagen-binding mixed micelles and their potential suitability to deliver therapeutic drugs to the vessel wall. We modified poly(ethylene oxide)-bl-poly(propylene oxide)-bl-poly(ethylene oxide) (Pluronic F-127) to display sulfate groups on the terminus of the PEO block to act as a heparin mimics and bind to collagen in the extracellular matrix. This functionalized macroamphiphile was incorporated into a mixed micelle with poly(propylene sulfide)-bl-poly(ethylene oxide), a macroamphiphile that demonstrates improved micellar stability relative to Pluronic F-127 micelles. The mixed micelles were examined using analytical ultracentrifugation, dynamic light scattering, transmission electron microscopy, and measures of the critical micellar concentration using surface tensiometry. Encapsulation and in vitro release of Sirolimus, an immunosuppressant drug of interest in coronary artery treatment, was considered as an example. Mixed micelles with the sulfate functionality demonstrated enhanced binding to collagen I coated surfaces, suggestive of the potential for binding to the extracellular milieu.

摘要

我们展示了胶原结合混合胶束的形成及其将治疗药物递送至血管壁的潜在适用性。我们对聚(环氧乙烷)-嵌段-聚(环氧丙烷)-嵌段-聚(环氧乙烷)(普朗尼克F-127)进行了修饰,使其在聚环氧乙烷嵌段末端显示硫酸基团,作为肝素模拟物并与细胞外基质中的胶原蛋白结合。这种功能化的大分子两亲物与聚(硫化丙烯)-嵌段-聚(环氧乙烷)形成混合胶束,聚(硫化丙烯)-嵌段-聚(环氧乙烷)是一种大分子两亲物,相对于普朗尼克F-127胶束,其胶束稳定性有所提高。使用分析超速离心、动态光散射、透射电子显微镜以及使用表面张力测定法测量临界胶束浓度对混合胶束进行了研究。以西罗莫司(一种在冠状动脉治疗中备受关注的免疫抑制药物)的包封和体外释放为例进行了研究。具有硫酸酯功能的混合胶束显示出与I型胶原包被表面的结合增强,这表明其具有与细胞外环境结合的潜力。

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