Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Drug Target. 2012 Nov;20(9):724-35. doi: 10.3109/1061186X.2012.719232. Epub 2012 Sep 20.
siRNA therapeutics has developed rapidly and already there are clinical trials ongoing or planned; however, the delivery of siRNA into cells, tissues or organs remains to be a major obstacle. Lipid-based vectors hold the most promising position among non-viral vectors, as they have a similar structure to cell or organelle membranes. But when used in the form of liposomes, these vectors have shown some problems. Therefore, either the nature of lipids themselves or forms used should be improved. As a novel class of lipid like materials, lipidoids have the advantages of easy synthesis and the ability for delivering siRNA to obtain excellent silencing activity. However, the toxicities of lipidoids have not been thoroughly studied. pH responsive lipids have also gained great attention recently, though some of the amine-based lipids are not novel in terms of chemical structures. More complex self-assembly structures, such as LPD (LPH) and LCP, may provide a good solution to siRNA delivery. They have demonstrated controlled particle morphology and size and siRNA delivery activity for both in vitro and in vivo.
siRNA 疗法发展迅速，目前已有临床试验正在进行或计划进行；然而，将 siRNA 递送到细胞、组织或器官仍然是一个主要障碍。在非病毒载体中，基于脂质的载体具有最有前途的地位，因为它们的结构与细胞膜或细胞器膜相似。但是，当以脂质体的形式使用时，这些载体显示出一些问题。因此，要么改善脂质本身的性质，要么改善所用的形式。作为一类新型的脂质样材料，脂质体具有易于合成和能够将 siRNA 递送到获得优异沉默活性的优点。然而，脂质体的毒性尚未得到彻底研究。pH 响应脂质最近也引起了极大的关注，尽管有些基于胺的脂质在化学结构上并不是新的。更复杂的自组装结构，如 LPD（LPH）和 LCP，可能为 siRNA 递供了一个很好的解决方案。它们已经证明了对体外和体内的 siRNA 递和活性具有控制的颗粒形态和大小。
