Division of Biomolecular Chemistry, Institute for Materials Chemistry and Engineering, Kyushu University, 744 Moto-oka, Nishi-ku, Fukuoka, 819-0395, Japan.
J Biomater Sci Polym Ed. 2013;24(10):1277-90. doi: 10.1080/09205063.2012.755600. Epub 2013 Jan 2.
Localized and sustained delivery of the therapeutic genes using a solid carrier matrix is a potential approach to develop highly curative treatments. Electrospun nanofiber mesh of biodegradable polymer has been applied extensively as a carrier for localized and sustained delivery of drugs, proteins, and DNA, but it remains difficult to release sufficient amounts of DNA while maintaining structural and functional integrity. To realize the stable sustained release of the healthy plasmid DNA (pDNA) from electrospun fiber mesh, a novel method was examined for loading pDNA into the fibers based on solid-in-oil (S/O) nanodispersion of pDNA in organic solvent for electrospinning polymer solution: S/O nanodispersion electrospinning. A prepared pDNA-loaded fiber mesh made of biodegradable polymer showed sustained release of pDNA without burst release. From luciferase activity-based in vitro transcription-translation assay, pDNA released from meshes of the S/O nanodispersion retained about 60% luciferase activity of control pDNA, whereas pDNA released from the meshes of simple mixing showed only about 5% activity, indicating that S/O nanodispersion electrospinning is effective for loading pDNA into electrospun fiber meshes while maintaining their healthy functions. Effectiveness of S/O nanodispersion electrospinning was verified for fabricating a sustained release carrier matrix for high molecular weight bioactives, including therapeutic genes.
使用固体载体基质进行局部和持续的治疗基因传递是开发高疗效治疗方法的一种潜在方法。可生物降解聚合物的静电纺纳米纤维网已广泛用作药物、蛋白质和 DNA 的局部和持续传递载体，但仍然难以在保持结构和功能完整性的同时释放足够量的 DNA。为了实现健康质粒 DNA（pDNA）从静电纺纤维网的稳定持续释放，研究了一种新的方法，即将 pDNA 加载到纤维中，方法是将 pDNA 在有机溶剂中的固体-油（S/O）纳米分散体用于静电纺丝聚合物溶液：S/O 纳米分散体静电纺丝。由可生物降解聚合物制成的负载 pDNA 的纤维网显示出 pDNA 的持续释放，没有突释。从基于荧光素酶活性的体外转录-翻译测定，从 S/O 纳米分散体的纤维网中释放的 pDNA 保留了对照 pDNA 的约 60%的荧光素酶活性，而从简单混合的纤维网中释放的 pDNA 仅显示约 5%的活性，表明 S/O 纳米分散体静电纺丝对于将 pDNA 加载到静电纺纤维网中同时保持其健康功能是有效的。S/O 纳米分散体静电纺丝的有效性已通过制造包括治疗基因在内的高分子生物活性物质的缓释载体基质得到验证。
