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通过在水相和生物介质中的分形分析描绘带电脂质体载体的形态:物理化学和自组装研究。

The delineation of the morphology of charged liposomal vectors via a fractal analysis in aqueous and biological media: physicochemical and self-assembly studies.

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Athens, Panepistimioupolis Zografou, 15771 Athens, Greece.

出版信息

Int J Pharm. 2012 Nov 1;437(1-2):264-74. doi: 10.1016/j.ijpharm.2012.08.017. Epub 2012 Aug 19.

DOI:10.1016/j.ijpharm.2012.08.017
PMID:22939965
Abstract

The present study deals with the physicochemical characterization of DPPC:DPPG (9:1 molar ratio) and DPPC:DODAP (9:1 molar ratio) liposomes, and the determination of their fractal dimension in HPLC-grade water, PBS and in FBS. Light scattering techniques were used in order to extract information on the structure, morphology, size and surface charge of liposomes in an ageing study and their structural response to changes in concentration and temperature. Fluorescence spectroscopy showed that the microviscosity of cationic liposomes changed by an increase of temperature. The fractal dimension, d(f), was found equal to 1.8 for reconstituted DPPC:DPPG (9:1) and DPPC:DODAP (9:1) liposomes in aqueous media. Aggregation of reconstituted DPPC:DPPG (9:1) and DPPC:DODAP (9:1) liposomes in FBS was observed. Their fractal dimensions were 1.46 and 2.45, respectively. The first order aggregation kinetics of DPPC:DODAP (9:1) liposomes in the presence of serum proteins was determined; the aggregates of cationic liposomes with serum components remained stable during 20 days with fractal dimension 2.5. The responsiveness of cationic liposomes to changes in temperature in the three dispersion media has revealed the self-assembly and the morphological complexity of cationic vectors. Finally, we suggest that these studies could be used for developing effective advanced drug delivery nano-systems (aDDnSs) based on their fractal characteristics which effectively draw their morphological profile.

摘要

本研究对 DPPC:DPPG(9:1 摩尔比)和 DPPC:DODAP(9:1 摩尔比)脂质体的物理化学特性进行了研究,并测定了它们在 HPLC 级水、PBS 和 FBS 中的分形维数。光散射技术用于在老化研究中提取关于脂质体结构、形态、大小和表面电荷的信息,并研究其对浓度和温度变化的结构响应。荧光光谱表明,阳离子脂质体的微粘度随温度升高而变化。在水介质中,重构的 DPPC:DPPG(9:1)和 DPPC:DODAP(9:1)脂质体的分形维数 d(f) 被发现等于 1.8。在 FBS 中观察到重构的 DPPC:DPPG(9:1)和 DPPC:DODAP(9:1)脂质体的聚集。它们的分形维数分别为 1.46 和 2.45。确定了 DPPC:DODAP(9:1)脂质体在存在血清蛋白时的一级聚集动力学;带血清成分的阳离子脂质体的聚集体在 20 天内保持稳定,分形维数为 2.5。阳离子脂质体在三种分散介质中对温度变化的响应揭示了阳离子载体的自组装和形态复杂性。最后,我们建议可以根据它们的分形特征开发有效的先进药物输送纳米系统(aDDnSs),这些特征可以有效地描绘它们的形态轮廓。

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