一种新型聚乙二醇-黏土杂化物作为药物递送系统材料的制备:分散稳定性和缓释特性

Preparation of a novel PEG-clay hybrid as a DDS material: dispersion stability and sustained release profiles.

作者信息

Takahashi Tadahito, Yamada Yoshiaki, Kataoka Kazunori, Nagasaki Yukio

机构信息

Pre-venture Program, Japan Science and Technology Corporation, JST, Japan.

出版信息

J Control Release. 2005 Oct 20;107(3):408-16. doi: 10.1016/j.jconrel.2005.03.031.

Abstract

An advanced hybrid drug carrier has been developed using porous nanocrystals of a swelling clay mineral conjugated with a block copolymer containing poly(ethylene glycol) and polyamine segments. Synthetic hectorite (Laponite) modified with (alpha-acetal-poly(ethylene glycol)-block-[poly(2-(N,N-dimethylamino) ethyl methacrylate)] (Acetal-PEG-b-PAMA) produced a homogeneous dispersion of organic-inorganic hybrid in an aqueous solution, which showed flocculation-resistive properties with an elevated ionic strength. The zeta-potential measurement revealed that nonionic PEG brush layers are formed on the surface of the clay nanocrystals since negative charge of the clay surface was completely neutralized by the positive charge of the cationic PAMA segment and the entire surface charge is successfully shielded by the effect of nonionic PEG segment in the block copolymer. This charge neutralization is in good agreement with the dispersion stability in solutions of high ionic strength. The average particle size of the PEG-modified hybrid particle was estimated to be 120 nm by a dynamic light scattering (DLS) method. When pyrene was used as the model compound of hydrophobic drug, it was incorporated into the nanopore in the clay mineral without showing any remarkable expansion of the basal spacings. Fluorescence spectra and powder X-ray diffraction patterns demonstrated that pyrene molecules are captured in an amorphous state in the range of low pyrene content (<5%), while excimer formation was seen at the higher pyrene concentration (>5%). The PEG-clay hybrid act as a carrier for sustained release of hydrophobic substances due to the high affinity (K = 1.52 x 10(4)) between the drug and clay surface.

摘要

一种先进的混合药物载体已被开发出来,它是利用一种膨胀性粘土矿物的多孔纳米晶体与一种含有聚(乙二醇)和聚胺链段的嵌段共聚物共轭而成。用(α-缩醛-聚(乙二醇)-嵌段-[聚(甲基丙烯酸2-(N,N-二甲基氨基)乙酯)](缩醛-聚乙二醇-b-聚甲基丙烯酸二甲氨基乙酯)改性的合成锂皂石(锂蒙脱石)在水溶液中产生了有机-无机杂化物的均匀分散体,在离子强度升高时表现出抗絮凝性能。ζ电位测量表明,由于粘土表面的负电荷被阳离子聚甲基丙烯酸二甲氨基乙酯链段的正电荷完全中和,并且整个表面电荷被嵌段共聚物中非离子聚乙二醇链段的作用成功屏蔽,因此在粘土纳米晶体表面形成了非离子聚乙二醇刷层。这种电荷中和与高离子强度溶液中的分散稳定性良好吻合。通过动态光散射(DLS)方法估计,聚乙二醇改性杂化颗粒的平均粒径为120nm。当芘用作疏水性药物的模型化合物时,它被掺入粘土矿物的纳米孔中,而没有显示出任何明显的基面间距扩展。荧光光谱和粉末X射线衍射图谱表明,在芘含量较低(<5%)的范围内,芘分子以无定形状态被捕获,而在芘浓度较高(>5%)时则观察到准分子形成。由于药物与粘土表面之间具有高亲和力(K = 1.52 x 10(4)),聚乙二醇-粘土杂化物可作为疏水性物质持续释放的载体。

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