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Fabrication of Nanoparticles by Gamma-ray crosslinking of thermosensitive polypeptides and analysis for controled release of drugs

通过热敏多肽的伽马射线交联制备纳米粒子以及药物控制释放的分析

基本信息

批准号：
18560803
负责人：
FURUTA Masakazu
金额：
$ 2.51万
依托单位：
Osaka Prefecture University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18560803/
关键词：
Nano materials Thermosensitivity Polypeptide Radiation Crosslinking

项目摘要

Elastin is an essential component in animal tissues as well as collagen. Elastin molecules are formed by covalent bounds of a cross-linked network and their network can stretch and recoil like rubber band. This elasticity conform a flexibility to such as skin, blood vessels, and lungs, need to this elasticity in order to function [6]. Elastin molecules are composed largely of hydrophobic amino acid residues, such as glycine (G) ,alanine (A) ,proline (P) and valine (V) and their amino acids repeat as (GVGVP)n exist in the animals. On raising the temperature, they folded and assembled above a specific temperature called cloud point (CP) and it formed helical structure of type II beta-turn. Using these hydrophobic amino acid residues, unique thermoresponsive polypeptides: poly [(GVGVP)_<251>]was synthesized by Urry, et al. using Escherichia coli recombinant DNA technology and these polypeptides exhibit a remarkable biocompatibility. Utilizing these thermosensitive polypeptides, Nanoparticles were prepared utilizing the thermosensitive aggregation of the elastin model polypeptides; poly[(GVGVP)_<251>]and gamma-ray crosslinking. Three different heating methods, "Slow heating", "Fast heating", and "Heat shock", were applied for the aggregation of the peptide and examined to yield stable nanoparticles by gamma-ray crosslinking. As a result, only "heat shock" procedure yielded stable nanoparticles with diameters of less than ca. 150 nm and a narrow size distribution. CD spectrometry showed that this polypeptide formed type II beta-turn structure on raising temperature above cloud point(CP)with the "heat shock" procedure and, kept the structure within the crosslinked nanoparticles, suggesting that this structure would be crucial to yield stable crosslinked particles.

弹性蛋白是动物组织和胶原蛋白的重要组成部分。弹性蛋白分子是由交联网络的共价键形成的，它们的网络可以像橡皮筋一样拉伸和反冲。这种弹性符合皮肤、血管和肺等的弹性，它们需要这种弹性才能发挥功能。弹性蛋白分子主要由疏水氨基酸残基组成，如甘氨酸(G)、丙氨酸(A)、脯氨酸(P)和缬氨酸(V)，它们的氨基酸重复为（GVGVP）n在动物体内存在。当温度升高时，它们在一个特定的云点（CP）以上折叠和组装，形成II型β转的螺旋结构。Urry等利用这些疏水氨基酸残基，利用大肠杆菌重组DNA技术合成了独特的热响应多肽：poly [(GVGVP)_<251>]，这些多肽具有良好的生物相容性。利用这些热敏多肽，利用弹性蛋白模型多肽的热敏聚集制备纳米颗粒；聚[(GVGVP)_<251>]和伽马射线交联。采用“慢速加热”、“快速加热”和“热冲击”三种不同的加热方法对肽进行聚集，并通过伽马射线交联检测产生稳定的纳米颗粒。因此，只有“热冲击”过程才能产生直径小于约150纳米且尺寸分布窄的稳定纳米颗粒。CD谱分析表明，该多肽在“热冲击”过程中，当温度高于云点（CP）时，形成II型β转结构，并保持了交联纳米颗粒内的结构，表明该结构对产生稳定的交联颗粒至关重要。