Transfection efficacy and drug release depends upon the PEG derivative in cationic lipoplexes: Evaluation in 3D in vitro model and in vivo

纳米载体 体内 脂质体 转染 PEG比率 体外 阳离子脂质体 化学 细胞毒性 生物物理学 分子生物学 药理学 药物输送 生物化学 生物 生物技术 财务 基因 经济 有机化学
作者
A. M. Gileva,О. О. Колоскова,A. S. Nosova,L.I. Vishniakova,V. A. Simonova,L. A. Kurbanova,Е. А. Егоренков,Smirnov Vv,U. A. Budanova,Yu. L. Sebyakin,Н. Е. Сузина,Musa Khaitov,Елена Марквичева
出处
期刊:Journal of Biomedical Materials Research Part B [Wiley]
卷期号:111 (9): 1614-1628 被引量:3
标识
DOI:10.1002/jbm.b.35259
摘要

Abstract The goal of the study was to estimate transfection efficacy and drug release in function of the PEG derivative in cationic liposomes and lipoplexes in both 2D and 3D in vitro models as well as in a mouse model (in vivo). For this purpose, cationic PEGylated nanocarriers based on OrnOrnGlu(C 16 H 33 ) 2 lipopeptides were fabricated and characterized. The nanocarriers were loaded with DNA plasmid pGL3 or with siRNA targeting 5′‐UTR region of Hepatitis C virus, and their transfection efficacies were studied by luciferase test or by PCR technique, respectively. The pGL3‐lipoplexes containing PEG derivative b (6 mol % PEG) were selected as the most promising nanocarriers for further in vivo study. In vitro cytotoxicity assay of the pGL3‐lipoplexes with the PEG derivative b showed 2‐ and 1.5‐fold enhancements of IC 50 levels for HEK293T and HepG2 cells, respectively. Accumulation of the liposomes in the cells was studied by confocal microscopy using both 2D (monolayer culture) and 3D (multicellular spheroids) in vitro models. The PEGylated liposomes were found to penetrate cells more slowly than unmodified ones (without PEG). Thus, maximum liposomes in the HEK293T cells was observed after 1 and 3 h in the case of 2D and 3D in vitro models, respectively. Biodistribution study in mice showed that the PEGylated lipoplexes containing the PEG derivative b were eliminated from the bloodstream more slowly, namely with the doubled half‐life time, than unmodified ones. Thus, the enhanced transfection efficacy and prolonged drug release of the PEGylated lipoplexes containing the optimal PEG derivative was demonstrated. This approach could be promising for development of novel siRNA‐based drugs.
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