Extracellular matrix binding mixed micelles for drug delivery applications

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• 作者：Conlin P. O'Neil ; André ; J. van der Vlies ; Diana Velluto ; Christine W ; rey ; Davide Demurtas ; Jacques Dubochet ; Jeffrey A. Hubbell
• 关键词：Mixed micelles ; Drug delivery ; Block copolymers ; Sirolimus ; Extracellular matrix
• 刊名：Journal of Controlled Release
• 出版年：2009
• 出版时间：20 July 2009
• 年：2009
• 卷：137
• 期：2
• 页码：146-151
• 全文大小：477 K

文摘

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.