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聚(甘油基癸二酸酯)-脂肪酸酯作为多功能纳米载体:从纳米立方体形到椭球体形再到纳米球形。

Poly(glycerol adipate)-fatty acid esters as versatile nanocarriers: From nanocubes over ellipsoids to nanospheres.

机构信息

Institute of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany.

出版信息

J Control Release. 2012 Feb 28;158(1):156-64. doi: 10.1016/j.jconrel.2011.09.077. Epub 2011 Sep 25.

Abstract

Poly(glycerol adipate) (PGA) is a biodegradable polymer with promising features for nanoparticulate drug carrier systems. By acylation of PGA with fatty acids, composite systems with amphiphilic properties can be obtained. Variation of the fatty acid (laurate, stearate and behenate) and their substitution degrees lead to a wide range of different polymer structures. This strongly influences the aggregation of the polymer and thus the nature of the resulting colloidal system. Based on the modification of the interfacial deposition method, various self-stabilizing nanoparticles with defined sizes and narrow size distributions could be prepared. Non-spherical shapes (squares, pentagons) with an internal lamellar-like structure were observed for low substituted PGA-stearates. Higher substitution degrees lead to ellipsoidal or spherical particles. The size, charge, fluidity and polarity of the nanoparticles have been studied comprehensively by PCS, AF4, zeta potential measurements, DSC, NMR, TEM and fluorescence spectroscopy. The chain lengths of the attached fatty acids as well as their substitution degree substantially influence the physicochemical properties of the bulk polymers and the nanoparticles. With their diverse particle shapes and internal structures as well as their different thermal behavior, aggregate states and polarities, the systems offer promising possibilities as delivery systems for lipophilic, amphiphilic and water soluble drugs.

摘要

聚(甘油己二酸酯)(PGA)是一种具有生物降解性能的聚合物,在纳米药物载体系统方面具有广阔的应用前景。通过脂肪酸酰化 PGA,可以得到具有两亲性的复合体系。脂肪酸(月桂酸、硬脂酸和山嵛酸)及其取代度的变化导致了广泛的不同聚合物结构。这强烈影响聚合物的聚集,从而影响所得胶体系统的性质。基于界面沉积方法的修饰,可以制备具有不同粒径和较窄粒径分布的各种自稳定纳米粒子。低取代度的 PGA-硬脂酸盐形成具有内部层状结构的非球形形状(方形、五边形)。较高的取代度导致形成椭球形或球形颗粒。通过 PCS、AF4、ζ 电位测量、DSC、NMR、TEM 和荧光光谱法,全面研究了纳米粒子的尺寸、电荷、流动性和极性。附着脂肪酸的链长及其取代度对块状聚合物和纳米粒子的物理化学性质有很大的影响。由于其多样化的颗粒形状和内部结构以及不同的热行为、聚集状态和极性,这些系统为亲脂性、两亲性和水溶性药物的递药系统提供了有前景的可能性。

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