Development of a nanostructured DNA delivery scaffold via electrospinning of PLGA and PLA-PEG block copolymers
Development of a nanostructured DNA delivery scaffold via electrospinning of PLGA and PLA-PEG block copolymers
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DOI：
10.1016/s0168-3659(03)00097-x
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发表时间：
2003-04-29
影响因子：
10.8
通讯作者：
Hadjiargyrou, M
中科院分区：
文献类型：
--
作者：
Luu, YK;Kim, K;Hadjiargyrou, M
本工作利用静电纺丝技术制备合成聚合物/DNA复合支架，用于组织工程基因输送的治疗。支架是无纺布、纳米纤维、膜结构，主要由聚(丙交酯-乙交酯)无规共聚物和聚(D，L-丙交酯)-聚乙二醇嵌段共聚物(聚乳酸-聚乙二醇)组成。从支架中释放的质粒DNA在20天的研究期间持续释放，最大释放时间约为2小时。累积释放谱显示释放量约为初始负载DNA的68-80%。PLGA与聚乳酸-聚乙二醇嵌段共聚物比例的变化极大地影响了整体结构形态，以及DNA释放的速度和效率。结果表明，直接从这些电纺支架中释放的DNA确实是完整的，能够进行细胞转染，并成功地编码了蛋白β-半乳糖苷酶。在拉伸载荷下测试时，电纺聚合物/DNA复合支架的拉伸模数类似于35兆帕，初始应变类似于45%。这些数值接近皮肤和软骨的数值。综上所述，这项工作代表了第一次成功地展示了使用静电纺丝将质粒DNA整合到聚合物支架中。(C)2003 Elsevier Science B.V.保留所有权利。
The present work utilizes electrospinning to fabricate synthetic polymer/DNA composite scaffolds for therapeutic application in gene delivery for tissue engineering. The scaffolds are non-woven, nano-fibered, membranous structures composed predominantly of poly(lactide-co-glycolide) (PLGA) random copolymer and a poly(D,L-lactide)-poly(ethylene Glycol) (PLA-PEG) block copolymer. Release of plasmid DNA from the scaffolds was sustained over a 20-day study period, with maximum release occurring at similar to2 h. Cumulative release profiles indicated amounts released were approximately 68-80% of the initially loaded DNA. Variations in the PLGA to PLA-PEG block copolymer ratio vastly affected the overall structural morphology, as well as both the rate and efficiency of DNA release. Results indicated that DNA released directly from these electrospun scaffolds was indeed intact, capable of cellular transfection, and successfully encoded the protein beta-galactosidase. When tested under tensile loads, the electrospun polymer/DNA composite scaffolds exhibited tensile moduli of similar to35 MPa, with similar to45% strain initially. These values approximate those of skin and cartilage. Taken together, this work represents the first successful demonstration of plasmid DNA incorporation into a polymer scaffold using electrospinning. (C) 2003 Elsevier Science B.V. All rights reserved.