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用于质粒DNA递送的聚(ε-己内酯)-聚(乙二醇)-聚(ε-己内酯)纳米颗粒的一步法制备

One-step preparation of poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) nanoparticles for plasmid DNA delivery.

作者信息

Huang Mei Juan, Gou Ma Ling, Qian Zhi Yong, Dai Mei, Li Xing Yi, Cao Mei, Wang Ke, Zhao Jian, Yang Jing Liang, Lu You, Tu Ming Jing, Wei Yu Quan

机构信息

State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.

出版信息

J Biomed Mater Res A. 2008 Sep 15;86(4):979-86. doi: 10.1002/jbm.a.31704.

DOI:10.1002/jbm.a.31704
PMID:18067161
Abstract

In this article, a kind of biodegradable poly(epsilon-caprolactone)-Poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) copolymer was synthesized by ring-opening polymerization method. The PCEC nanoparticles were prepared at one-step by modified emulsion solvent evaporation method using CTAB as stabilizer. With increase in PCEC concentration, the particle size increased obviously, but zeta potential only increased slightly. The obtained cationic PCEC nanoparticle was employed to condense and adsorb DNA onto its surface. Plasmid GFP (pGFP) was used as model plasmid to evaluate the loading capacity of cationic PCEC nanoparticles in this work. The DNA/nanoparticles weight ratio at 1:16 induced almost neutral zeta potential of DNA-nanoparticles complex. At this time, the size of complex became abnormally large which implied aggregates formed. So DNA-nanoparticles weight ratio should be chosen carefully. The cationic PCEC nanoparticles had the capacity of condensing plasmid DNA into complex when the DNA/nanoparticles weight ratio was lower than 1:8, which was evidenced by gel retardation assay. In vitro release behavior of DNA/nanoparticle complexes was also studied here. The obtained cationic PCEC nanoparticles might have great potential application in DNA delivery.

摘要

在本文中,通过开环聚合法合成了一种可生物降解的聚(ε-己内酯)-聚(乙二醇)-聚(ε-己内酯)(PCL-PEG-PCL,PCEC)共聚物。以十六烷基三甲基溴化铵(CTAB)为稳定剂,采用改进的乳液溶剂蒸发法一步制备了PCEC纳米颗粒。随着PCEC浓度的增加,粒径明显增大,但zeta电位仅略有增加。将所得的阳离子PCEC纳米颗粒用于在其表面凝聚和吸附DNA。在本研究中,使用质粒绿色荧光蛋白(pGFP)作为模型质粒来评估阳离子PCEC纳米颗粒的负载能力。DNA/纳米颗粒重量比为1:16时,DNA-纳米颗粒复合物的zeta电位几乎呈中性。此时,复合物的尺寸变得异常大,这意味着形成了聚集体。因此,应谨慎选择DNA-纳米颗粒的重量比。当DNA/纳米颗粒重量比低于1:8时,阳离子PCEC纳米颗粒具有将质粒DNA凝聚成复合物的能力,这通过凝胶阻滞试验得到了证实。本文还研究了DNA/纳米颗粒复合物的体外释放行为。所得的阳离子PCEC纳米颗粒在DNA递送方面可能具有巨大的潜在应用价值。

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