Storage stability of optimal liposome-polyethylenimine complexes (lipopolyplexes) for DNA or siRNA delivery
Storage stability of optimal liposome-polyethylenimine complexes (lipopolyplexes) for DNA or siRNA delivery
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DOI：
10.1016/j.actbio.2014.02.037
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发表时间：
2014-06-01
影响因子：
9.7
通讯作者：
Aigner, Achim
中科院分区：
文献类型：
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作者：
Ewe, Alexander;Schaper, Andreas;Aigner, Achim
DNA或siRNA等核酸的输送仍然是一个主要障碍，特别是在体内可能的治疗应用方面。非病毒基因递送载体，包括脂质体或阳离子聚合物的发展引起了人们的极大关注。其中，聚乙烯亚胺(PEI)作为核酸载体已被广泛研究，并显示出良好的应用前景。阳离子聚合物和脂质体(脂多糖)结合了脂类系统(高稳定性、有效的细胞摄取、低细胞毒性)和PEIS(核酸凝聚，促进内体释放)的有利性质，可以进一步提高其有效性和生物相容性。在本研究中，我们从生物活性(DNA转染率、siRNA敲除效率)和理化性质(大小、Zeta电位、稳定性)等方面系统地分析了制备脂质体-聚乙烯亚胺类脂多糖的各种条件。这包括探索含有不同脂质体和不同相关支链或线状低分子PEI的脂多糖组合物。我们根据不同的PEI、N/P比、脂类、脂/PEI比和制备条件，建立了产生脂多糖体的最佳参数。重要的是，我们还证明，某些脂多糖在长时间储存后，即使在37摄氏度和/或有血清存在的情况下，也能保持其生物活性和物理化学完整性，因此提供的制剂比聚合物具有相当高的稳定性。总之，我们建立了允许在环境条件下储存的最佳脂质体-聚乙烯亚胺脂多糖体。这是为可能的治疗应用开发新的、有前景的和易于处理的配方的基础和基本前提。(C)2014 Acta Materialia Inc.由Elsevier Ltd.出版。保留所有权利。
The delivery of nucleic acids such as DNA or siRNA still represents a major hurdle, especially with regard to possible therapeutic applications in vivo. Much attention has been focused on the development of non-viral gene delivery vectors, including liposomes or cationic polymers. Among them, polyethylenimines (PEIs) have been widely explored for the delivery of nucleic acids and show promising results. The combination of cationic polymers and liposomes (lipopolyplexes) for gene delivery may further improve their efficacy and biocompatibility, by combining the favourable properties of lipid systems (high stability, efficient cellular uptake, low cytotoxicity) and PEIs (nucleic acid condensation, facilitated endosomal release). In this study, we systematically analyse various conditions for the preparation of liposome-polyethylenimine-based lipopolyplexes with regard to biological activity (DNA transfection efficacy, siRNA knockdown efficacy) and physicochemical properties (size, zeta potential, stability). This includes the exploration of lipopolyplex compositions containing different liposomes and different relevant branched or linear low-molecular-weight PEIs. We establish optimal parameters for lipopolyplex generation, based on various PEIs, N/P ratios, lipids, lipid/PEI ratios and preparation conditions. Importantly, we also demonstrate that certain lipopolyplexes retain their biological activity and physicochemical integrity upon prolonged storage, even at 37 degrees C and/or in the presence of serum, thus providing formulations with considerably higher stability as compared to polyplexes. In conclusion, we establish optimal liposome-polyethylenimine lipopolyplexes that allow storage under ambient conditions. This is the basis and an essential prerequisite for novel, promising and easy-to-handle formulations for possible therapeutic applications. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.