PDF(Pubmed)
Abstract：
This study aimed to develop polyvinyl alcohol (PVA) nanofibers encapsulating 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/siRNA complexes via electrospinning for the delivery of nucleic acid-based drugs. It also focused on the influence of the intrinsic properties of PVA on the efficacy of the system. PVA nanofibers, with diameters of 300-400 nm, were obtained, within which the siRNA remained intact and the DOTAP/siRNA complexes were uniformly dispersed. By incorporating DOTAP/siRNA complexes into the PVA nanofibers and assessing the impact of their RNA interference (RNAi) activity in A549-Luc cells, a stable inhibition of luciferase expression was observed. An examination of the nanofiber preparation process revealed that even when DOTAP or siRNA were added separately to the PVA solution without forming complexes, the RNAi effect was retained. The DOTAP/siRNA complexes released from the PVA nanofibers were internalized by the cells, with some PVA residues remaining on their surfaces. The significance of the degree of hydrolysis and polymerization of PVA on the performance of nanofibers was highlighted. Notably, PVA with a low degree of hydrolysis substantially enhanced RNAi effects, with luciferase expression inhibition reaching 91.5 ± 0.7%. Nanofibers made of PVA grades with anionic or cationic modifications were also evaluated, suggesting that they affect the efficacy of siRNA delivery. The insights obtained suggest avenues for future research to optimize drug delivery systems further.
摘要：
这项研究旨在开发通过静电纺丝封装1,2-二油酰基-3-三甲基铵-丙烷（DOTAP）/siRNA复合物的聚乙烯醇（PVA）纳米纤维，用于递送基于核酸的药物。还重点研讨了PVA的内在性质对系统功效的影响。PVA纳米纤维，直径为300-400nm，获得了,其中siRNA保持完整并且DOTAP/siRNA复合物均匀分散。通过将DOTAP/siRNA复合物掺入PVA纳米纤维并评估其RNA干扰（RNAi）活性在A549-Luc细胞中的影响，观察到荧光素酶表达的稳定抑制。对纳米纤维制备过程的检查表明，即使将DOTAP或siRNA分别添加到PVA溶液中而不形成复合物，RNAi效应得以保留。从PVA纳米纤维释放的DOTAP/siRNA复合物被细胞内化，一些PVA残留物残留在它们的表面上。强调了PVA的水解度和聚合度对纳米纤维性能的影响。值得注意的是,低水解度PVA显著增强RNAi效果,荧光素酶表达抑制达到91.5±0.7%。还评估了由具有阴离子或阳离子改性的PVA等级制成的纳米纤维，这表明它们会影响siRNA递送的功效。获得的见解为进一步优化药物递送系统的未来研究提供了途径。
