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用氯喹和不同表面活性剂制备的脂质体的生物物理性质与其转染效率之间的相关性。

Correlation between Biophysical Properties of Niosomes Elaborated with Chloroquine and Different Tensioactives and Their Transfection Efficiency.

作者信息

Sainz-Ramos Myriam, Villate-Beitia Ilia, Gallego Idoia, Al Qtaish Nuseibah, Menéndez Margarita, Lagartera Laura, Grijalvo Santiago, Eritja Ramón, Puras Gustavo, Pedraz José Luis

机构信息

Laboratory of Pharmacy and Pharmaceutical Technology, NanoBioCel Research Group, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.

Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Av. Monforte de Lemos 3-5, 28029 Madrid, Spain.

出版信息

Pharmaceutics. 2021 Oct 26;13(11):1787. doi: 10.3390/pharmaceutics13111787.

Abstract

Lipid nanocarriers, such as niosomes, are considered attractive candidates for non-viral gene delivery due to their suitable biocompatibility and high versatility. In this work, we studied the influence of incorporating chloroquine in niosomes biophysical performance, as well as the effect of non-ionic surfactant composition and protocol of incorporation in their biophysical performance. An exhaustive comparative evaluation of three niosome formulations differing in these parameters was performed, which included the analysis of their thermal stability, rheological behavior, mean particle size, dispersity, zeta potential, morphology, membrane packing capacity, affinity to bind DNA, ability to release and protect the genetic material, buffering capacity and ability to escape from artificially synthesized lysosomes. Finally, in vitro biological studies were, also, performed in order to determine the compatibility of the formulations with biological systems, their transfection efficiency and transgene expression. Results revealed that the incorporation of chloroquine in niosome formulations improved their biophysical properties and the transfection efficiency, while the substitution of one of the non-ionic surfactants and the phase of addition resulted in less biophysical variations. Of note, the present work provides several biophysical parameters and characterization strategies that could be used as gold standard for gene therapy nanosystems evaluation.

摘要

脂质纳米载体,如非离子型表面活性剂泡囊,由于其良好的生物相容性和高度的多功能性,被认为是极具吸引力的非病毒基因递送候选物。在本研究中,我们研究了将氯喹掺入非离子型表面活性剂泡囊对其生物物理性能的影响,以及非离子表面活性剂组成和掺入方案对其生物物理性能的影响。对在这些参数上不同的三种非离子型表面活性剂泡囊制剂进行了详尽的比较评估,包括对其热稳定性、流变行为、平均粒径、分散性、zeta电位、形态、膜堆积能力、结合DNA的亲和力、释放和保护遗传物质的能力、缓冲能力以及从人工合成溶酶体中逃逸的能力的分析。最后,还进行了体外生物学研究,以确定制剂与生物系统的相容性、转染效率和转基因表达。结果表明,在非离子型表面活性剂泡囊制剂中掺入氯喹可改善其生物物理性质和转染效率,而一种非离子表面活性剂的替代和添加阶段导致较小的生物物理变化。值得注意的是,本研究提供了几个生物物理参数和表征策略,可作为基因治疗纳米系统评估的金标准。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de28/8623750/b9fde727875b/pharmaceutics-13-01787-g001.jpg

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