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载有 Sp H1-DNA 复合物的白蛋白微球的研制:一种新型基因传递系统。

Development of albumin microspheres containing Sp H1-DNA complexes: a novel gene delivery system.

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA 30341, USA.

出版信息

J Microencapsul. 2010;27(2):142-9. doi: 10.3109/02652040903052028.

Abstract

This study investigated the stability and transfection efficiency of plasmid DNA (pDNA) and sea urchin sperm histone H1 (Sp H1) complexes embedded in albumin microsphere formulations. Sp H1 increased the stability and transfection efficiency of pDNA, while providing a favourable sustained pDNA release profile. Encapsulating Sp H1-complexed pDNA into albumin microspheres further protected the pDNA from physical stress and heparin treatment. When compared with free pDNA encapsulated in albumin microspheres, the Sp H1-pDNA microsphere formulations exhibited decreased hydrophilicity, slower pDNA release profiles, protection against heparin-induced degradation of embedded pDNA and increased stability against physical stress. These results indicate that complex formation of pDNA with Sp H1 facilitates intracellular DNA transfer and that albumin microspheres-Sp H1-pDNA gene delivery formulations are suitable for controlled-release delivery of pDNA while offering protection of the pDNA from degradation and maintaining pDNA biological activity.

摘要

本研究考察了包埋在白蛋白微球制剂中的质粒 DNA(pDNA)和海胆精子组蛋白 H1(Sp H1)复合物的稳定性和转染效率。Sp H1 提高了 pDNA 的稳定性和转染效率,同时提供了有利的持续 pDNA 释放曲线。将 Sp H1-复合 pDNA 包埋在白蛋白微球中进一步保护 pDNA 免受物理压力和肝素处理的影响。与包埋在白蛋白微球中的游离 pDNA 相比,Sp H1-pDNA 微球制剂表现出较低的亲水性、较慢的 pDNA 释放曲线、对肝素诱导的包埋 pDNA 降解的保护以及对物理应激的稳定性增加。这些结果表明,pDNA 与 Sp H1 的复合物形成有助于细胞内 DNA 转移,并且白蛋白微球-Sp H1-pDNA 基因传递制剂适合于 pDNA 的控释递送,同时保护 pDNA 免受降解并维持 pDNA 的生物学活性。

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