SET's College of Pharmacy, Department of Pharmacology, Dharwad, India.
Expert Opin Drug Deliv. 2011 Nov;8(11):1455-68. doi: 10.1517/17425247.2011.610790. Epub 2011 Aug 26.
The discovery of synthetic small interfering RNA (siRNA) has led to a surge of interest in harnessing RNA interference (RNAi) technology for biomedical applications and drug development. Even though siRNA can be a powerful therapeutic drug, its delivery remains a major challenge, due to the difficulty in its cellular uptake. Naked siRNA has a biological half-life of less than an hour in human plasma. To increase the lifetime and improve its therapeutic efficacy, non-viral vectors have been developed. As a natural evolution, cyclodextrins (CDs), which are natural cyclic oligosaccharides, have recently been applied as delivery vehicles for siRNA, and this in turn, has led to a surge of interest in this area.
This review discusses the recent advances made in the design of delivery strategies for siRNA, focusing on CD-based delivery vectors, because these have demonstrated clinical success. The methods of preparation of CD-based vectors, their characterization, transfection efficiencies, cellular toxicity, preclinical and clinical trials are also addressed, as well as future therapeutic applications.
siRNA-mediated RNAi therapeutics is beginning to transform healthcare, particularly, for the treatment of solid tumors. For example, CALAA01, a targeted, self-assembling nanoparticle system based on CD complexed with siRNA has been effective in phase I clinical trials. Although siRNA therapeutics suffers from problems related to off-target effects and non-specific gene silencing, these problems can be overcome by reducing the nanoparticle size, improving the targeting efficiency and by modifying the primary sequence of the siRNA.
合成小干扰 RNA（siRNA）的发现引发了人们对利用 RNA 干扰（RNAi）技术进行生物医学应用和药物开发的浓厚兴趣。尽管 siRNA 可以作为一种强大的治疗药物，但由于其细胞摄取困难，其递送仍然是一个主要挑战。裸 siRNA 在人血浆中的生物半衰期不到一个小时。为了增加半衰期并提高其治疗效果，已经开发了非病毒载体。作为一种自然进化，最近已将环糊精（CD）作为 siRNA 的递送载体应用，这反过来又引发了该领域的研究热潮。
本综述讨论了设计 siRNA 递送策略的最新进展，重点介绍了基于 CD 的递送载体，因为这些载体已经证明了临床成功。还讨论了基于 CD 的载体的制备方法、表征、转染效率、细胞毒性、临床前和临床试验以及未来的治疗应用。
siRNA 介导的 RNAi 疗法开始改变医疗保健，特别是用于治疗实体瘤。例如，CALAA01 是一种基于与 siRNA 复合的 CD 的靶向自组装纳米颗粒系统，已在 I 期临床试验中有效。尽管 siRNA 疗法存在与脱靶效应和非特异性基因沉默相关的问题，但通过减小纳米颗粒尺寸、提高靶向效率和修饰 siRNA 的原始序列，可以克服这些问题。
