Ewe Alexander, Aigner Achim
Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Härtelstrasse 16-18, 04107, Leipzig, Germany.
Methods Mol Biol. 2016;1445:187-200. doi: 10.1007/978-1-4939-3718-9_12.
The delivery of nucleic acids (NA) like DNA for cell transfection or siRNAs for gene knockdown is of major interest for in vitro studies as well as for applications in vivo. The same is true for other small RNA molecules like miRNAs or miRNA inhibitors (antimiRs). Important nonviral gene delivery vectors include liposomes and cationic polymers. With regard to cationic polymers, polyethylenimines (PEIs) are well established for the delivery of NA, by acting as nanoscale delivery platforms (polyplexes). Their combination with liposomes comprising different phospholipids leads to the formation of lipopolyplexes and can further improve their efficacy and biocompatibility, by combining the favorable properties of lipid systems (high stability, efficient cellular uptake, low cytotoxicity) and PEI (NA condensation, facilitated endosomal release).In this chapter, optimal lipopolyplex compositions containing different liposomes and certain branched or linear low-molecular weight PEIs are given. This also includes optimal parameters for lipopolyplex generation, based on various PEIs, N/P ratios, lipids, lipid/PEI ratios, and preparation conditions.Importantly, certain lipopolyplexes retain their biological activity and physicochemical integrity upon prolonged storage at room temperature (RT), in the presence of serum and upon nebulization, thus extending their usefulness toward various applications in vivo.
用于细胞转染的核酸（如DNA）或用于基因敲除的小干扰RNA（siRNA）的递送，对于体外研究以及体内应用都具有重要意义。对于其他小RNA分子，如微小RNA（miRNA）或miRNA抑制剂（抗miR）来说也是如此。重要的非病毒基因递送载体包括脂质体和阳离子聚合物。就阳离子聚合物而言，聚乙烯亚胺（PEI）作为纳米级递送平台（多聚体），在核酸递送方面已得到广泛应用。将其与包含不同磷脂的脂质体相结合，可形成脂质多聚体，通过结合脂质系统（高稳定性、高效细胞摄取、低细胞毒性）和PEI（核酸凝聚、促进内体释放）的有利特性，可进一步提高其功效和生物相容性。在本章中，给出了包含不同脂质体以及某些支链或线性低分子量PEI的最佳脂质多聚体组合物。这还包括基于各种PEI、氮/磷比、脂质、脂质/PEI比和制备条件的脂质多聚体生成的最佳参数。重要的是，某些脂质多聚体在室温（RT）下长时间储存、存在血清以及雾化后仍能保持其生物活性和物理化学完整性，从而扩展了它们在体内各种应用中的用途。
