PDF(Pubmed)
Abstract：
In this study, we use modified cationic nanocarriers as vehicles for the intracellular delivery of therapeutic siRNA. After developing nanocarrier formulations with appropriate pKa, size, swellability, and cytocompatibility, we investigated the importance of siRNA loading methods by studying the impact of the pH and time over which siRNA is loaded into the nanocarriers. We concentrate on diffusion-based loading in the presence and absence of electrostatic interactions. siRNA release kinetics were studied using samples prepared from nanocarriers loaded by both mechanisms. In addition, siRNA delivery was evaluated for two formulations. While previous studies were conducted with samples prepared by siRNA loading at low pH values, this research provides evidence that loading conditions of siRNA affect the release behavior. This study concludes that this concept could prove advantageous for eliciting prolonged intracellular release of nucleic acids and negatively charged molecules, effectively decreasing dose frequency and contributing to more effective therapies and improved patient outcomes. In addition, our findings could be leveraged for enhanced control over siRNA release kinetics, providing novel methods for the continued optimization of cationic nanoparticles in a wide array of RNA interference-based applications.
摘要：
在这项研究中,我们使用修饰的阳离子纳米载体作为细胞内递送治疗性siRNA的载体。在开发具有适当pKa的纳米载体制剂后，尺寸,膨胀性,和细胞相容性，我们通过研究pH值和siRNA加载到纳米载体中的时间的影响,研究了siRNA加载方法的重要性.我们专注于在存在和不存在静电相互作用的情况下基于扩散的负载。使用由两种机制加载的纳米载体制备的样品研究siRNA释放动力学。此外,评估两种制剂的siRNA递送。虽然以前的研究是在低pH值下通过siRNA加载制备的样品进行的，本研究提供了siRNA加载条件影响释放行为的证据。这项研究得出的结论是，这个概念可以证明有利于引发核酸和带负电荷的分子的延长细胞内释放，有效地减少剂量频率，并有助于更有效的治疗和改善患者的结果。此外,我们的发现可以用于增强对siRNA释放动力学的控制，提供了在一系列基于RNA干扰的应用中持续优化阳离子纳米颗粒的新方法。
