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从可生物降解聚合物药物递送膜中释放蛋白质药物的定量飞行时间二次离子质谱研究

Quantitative ToF-SIMS Studies of Protein Drug Release from Biodegradable Polymer Drug Delivery Membranes.

作者信息

Burns Sarah A, Gardella Joseph A

机构信息

Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY, 14260-3000 USA.

出版信息

Appl Surf Sci. 2008 Dec 15;255(4):1170-1173. doi: 10.1016/j.apsusc.2008.05.082.

Abstract

Biodegradable polymers are of interest in developing strategies to control protein drug delivery. The protein that was used in this study is Keratinocyte Growth Factor (KGF) which is a protein involved in the re-epithelialization process. The protein is stabilized in the biodegradable polymer matrix during formulation and over the course of polymer degradation with the use of an ionic surfactant Aerosol-OT (AOT) which will encapsulate the protein in an aqueous environment. The release kinetics of the protein from the surface of these materials requires precise timing which is a crucial factor in the efficacy of this drug delivery system.Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) was used in the same capacity to identify the molecular ion peak of the surfactant and polymer and use this to determine surface concentration. In the polymer matrix, the surfactant molecular ion peak was observed in the positive and negative mode at m/z 467 and 421, respectively. These peaks were determined to be [AOT + Na+] and [AOT-Na+]-. These methods are used to identify the surfactant and protein from the polymer matrix and are used to measure the rate of surface accumulation. The second step was to compare this accumulation rate with the release rate of the protein into an aqueous solution during the degradation of the biodegradable film. This rate is compared to that from fluorescence spectroscopy measurements using the protein autofluorescence from that released into aqueous solution.

摘要

可生物降解聚合物在开发控制蛋白质药物递送的策略方面备受关注。本研究中使用的蛋白质是角质形成细胞生长因子(KGF),它是一种参与再上皮化过程的蛋白质。在制剂过程中以及在聚合物降解过程中,利用离子表面活性剂气溶胶-OT(AOT)将蛋白质稳定在可生物降解的聚合物基质中,该表面活性剂会在水性环境中包裹蛋白质。蛋白质从这些材料表面的释放动力学需要精确的时间控制,这是该药物递送系统疗效的关键因素。飞行时间二次离子质谱(ToF-SIMS)以同样的方式用于识别表面活性剂和聚合物的分子离子峰,并以此确定表面浓度。在聚合物基质中,分别在正离子模式和负离子模式下于m/z 467和421处观察到表面活性剂分子离子峰。这些峰被确定为[AOT + Na+]和[AOT-Na+]-。这些方法用于从聚合物基质中识别表面活性剂和蛋白质,并用于测量表面积累速率。第二步是将这种积累速率与可生物降解薄膜降解过程中蛋白质释放到水溶液中的速率进行比较。该速率与使用释放到水溶液中的蛋白质自身荧光进行荧光光谱测量得到的速率进行比较。

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