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调整万古霉素从β-磷酸三钙/琼脂糖支架中的释放。

Tailoring vancomycin release from beta-TCP/agarose scaffolds.

作者信息

Cabañas M V, Peña J, Román J, Vallet-Regí M

机构信息

Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.

出版信息

Eur J Pharm Sci. 2009 Jun 28;37(3-4):249-56. doi: 10.1016/j.ejps.2009.02.011. Epub 2009 Mar 5.

Abstract

In this work a multifaceted approach to the fabrication of scaffolds is considered, that is, besides the preparation technique, the introduction of substances that may contribute to enhance their final performance, as well as the techniques required to ensure the correct preservation of the so obtained scaffolds are taken into account to tailor the release of vancomycin from beta-tricalcium phosphate (beta-TCP)/agarose scaffolds. These materials were prepared by a shaping technique that allows to obtain pieces at a temperature low enough to simultaneously include active substances susceptible of heat degrading such as vancomycin, the model drug considered in this work. In the first approximation poly(ethylene glycol) (PEG), a hydrophilic substance employed as a matrix capable of binding compounds such as proteins or peptides and release them in a controlled fashion, was included in the formulation. The second tool to govern the vancomycin liberation is based on the drying procedures employed to process and preserve the obtained scaffolds: freeze-drying and heat desiccation at 37 degrees C. These modifications resulted in the generation of different pore architectures and certain chemical interactions, such as the formation of an agarose-PEG-vancomycin complex that yielded different drug release patterns. The so obtained pieces behave like a hydrogel when immersed in a hydrated medium but show a consistency comparable to that of the cancellous bone.

摘要

在这项工作中,我们考虑了一种多方面的支架制造方法,也就是说,除了制备技术外,还考虑引入可能有助于提高其最终性能的物质,以及确保正确保存如此获得的支架所需的技术,以调整万古霉素从β-磷酸三钙(β-TCP)/琼脂糖支架中的释放。这些材料是通过一种成型技术制备的,该技术能够在足够低的温度下获得块状物,以便同时包含易受热降解的活性物质,如万古霉素,这是本研究中所考虑的模型药物。在初步近似中,聚乙二醇(PEG)作为一种亲水性物质被用作基质,能够结合蛋白质或肽等化合物并以可控方式释放它们,被包含在配方中。控制万古霉素释放的第二个工具基于用于处理和保存所获得支架的干燥程序:冷冻干燥和37℃加热干燥。这些改性导致产生了不同的孔结构和某些化学相互作用,例如形成了琼脂糖-PEG-万古霉素复合物,从而产生了不同的药物释放模式。如此获得的块状物在浸入水合介质中时表现得像水凝胶,但显示出与松质骨相当的稠度。

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