Nebulization of liposome-polyethylenimine complexes (lipopolyplexes) for DNA or siRNA delivery: Physicochemical properties and biological activity

被引:14
作者
Ewe, Alexander [1 ]
Aigner, Achim [1 ]
机构
[1] Univ Leipzig, Rudolf Boehm Inst Pharmacol & Toxicol, D-04107 Leipzig, Germany
关键词
DNA and siRNA transfection; Lipopolyplex; Liposome; Nebulization; Polyethlyenimine; NUCLEIC-ACID DELIVERY; GENE DELIVERY; IN-VIVO; PLASMID DNA; AIRWAY EPITHELIUM; CELLS; PEI; TRANSFECTION; STABILITY; SYSTEMS;
D O I
10.1002/ejlt.201300404
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
The delivery of nucleic acids into the lung is still one major bottleneck and relies on the development of efficient non-viral carriers that can be nebulized for their direct administration. Liposomal formulations, including those comprising different phospholipids, have been intensively studied. Likewise, polyethylenimines (PEI) have been widely explored due to their ability to protect nucleic acids from degradation and mediate cellular uptake and endosomal/lysosomal release. The combination of PEIs and liposomes is a particularly intriguing concept, leading to enhanced transfection efficiencies, lower cytotoxicities, and protection from aggregation. We have previously established lipopolyplexes, comprising PEI F25-LMW and the neutral phospholipid DPPC with various colipids. However, nebulization shear forces may be problematic for lipid formulations and require the testing of lipopolyplexes. In this paper, we demonstrate that DNA-or siRNA-containing PEI-based lipopolyplexes are indeed stable toward nebulization and retain their physicochemical integrity and biological activity. DNA transfection efficacies, but not siRNA knockdown, of certain lipopolyplexes are even enhanced upon nebulization, and nebulized lipopolyplexes also allow storage. This is due to the preservation of lipopolyplex size and zeta potential upon nebulization. More detailed analyses also reveal a dependence on the lipid, the medium used for preparation, the PEI and the nucleic acid.
引用
收藏
页码:1195 / 1204
页数:10
相关论文
共 51 条
  • [21] Polyethylenimines for siRNA and miRNA delivery in vivo
    Hoebel, Sabrina
    Aigner, Achim
    [J]. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY, 2013, 5 (05) : 484 - 501
  • [22] A scalable, extrusion-free method for efficient liposomal encapsulation of plasmid DNA
    Jeffs, LB
    Palmer, LR
    Ambegia, EG
    Giesbrecht, C
    Ewanick, S
    MacLachlan, I
    [J]. PHARMACEUTICAL RESEARCH, 2005, 22 (03) : 362 - 372
  • [23] Modified polyethylenimines as non-viral gene delivery systems for aerosol gene therapy: investigations of the complex structure and stability during air-jet and ultrasonic nebulization
    Kleemann, E
    Dailey, LA
    Abdelhady, HG
    Gessler, T
    Schmehl, T
    Roberts, CJ
    Davies, MC
    Seeger, W
    Kissel, T
    [J]. JOURNAL OF CONTROLLED RELEASE, 2004, 100 (03) : 437 - 450
  • [24] Liposome encapsulated polyethylenimine/ODN polyplexes for brain targeting
    Ko, Young Tag
    Bhattacharya, Raktima
    Bickel, Ulrich
    [J]. JOURNAL OF CONTROLLED RELEASE, 2009, 133 (03) : 230 - 237
  • [25] Lai WF, 2011, EXPERT REV MED DEVIC, V8, P173, DOI [10.1586/erd.10.83, 10.1586/ERD.10.83]
  • [26] Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery
    Landen, CN
    Chavez-Reyes, A
    Bucana, C
    Schmandt, R
    Deavers, MT
    Lopez-Berestein, G
    Sood, AK
    [J]. CANCER RESEARCH, 2005, 65 (15) : 6910 - 6918
  • [27] Synergistic effect of polyethylenimine and cationic liposomes in nucleic acid delivery to human cancer cells
    Lee, CH
    Ni, YH
    Chen, CC
    Chou, CK
    Chang, FH
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2003, 1611 (1-2): : 55 - 62
  • [28] Polyethylenimine-based non-viral gene delivery systems
    Lungwitz, U
    Breunig, M
    Blunk, T
    Göpferich, A
    [J]. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2005, 60 (02) : 247 - 266
  • [29] Factors controlling particle size during nebulization of DNA-polycation complexes
    Lynch, J.
    Behan, N.
    Birkinshaw, Colin
    [J]. JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG, 2007, 20 (03): : 257 - 268
  • [30] Malek A, 2008, J DRUG TARGET, V16, P124, DOI [10.1080/10611860701849058, 10.1080/10611860701849058 ]