Cationic Liposome-Based Systems for Nucleic Acid Delivery: From the Formulation Development to Therapeutic Applications

  • Henrique Faneca
  • Ana Luísa Cardoso
  • Sara Trabulo
  • Sónia Duarte
  • Maria C. Pedroso de LimaEmail author
Part of the Advances in Predictive, Preventive and Personalised Medicine book series (APPPM, volume 4)


Significant progress has been made in the development of different types of nucleic acids, including plasmid DNA, siRNA and oligonucleotides with the potential to form the basis of new treatment options for genetic and acquired diseases. However, the lack of suitable vectors for efficient delivery of nucleic acids into target cells represents a major hurdle for the successful application of gene therapy.

Since they were first described by Felgner et al. in the late 1980s, cationic liposomes have been considered one of the most promising carriers for nucleic acid delivery to mammalian cells in vitro and in vivo. Nevertheless, cationic liposomes suffer from relatively low levels of gene expression, thus the drive to improve these vectors continues.

Here, we describe crucial physicochemical parameters of cationic liposome-based systems that modulate their biological activity. Moreover, we provide an overview of different strategies that have been explored to surpass cellular barriers towards improving the efficacy of these systems to mediate nucleic acid delivery and therapeutic activity. Finally, examples illustrating the application of cationic liposome-based systems in clinical trials are presented.

Graphical Abstract

Following binding to the plasma membrane of the target cell, lipoplexes are internalized by the endocytotic pathway. Once inside the endosome, lipoplexes promote endosomal membrane destabilization allowing nucleic acid delivery into the cytoplasm and subsequent nuclear translocation. All these steps are crucial for achieving efficient therapeutic activity


Nucleic acid delivery Cationic liposomes Lipoplexes Gene therapy Targeting ligands Personalized medicine 





Atopic dermatitis

Apo B

Apolipoprotein B


Antisense oligonucleotide


Blood brain barrier


Break cluster region-Abelson


Cytosine deaminase

CD4+ T lymphocytes

T lymphocytes expressing the cluster differentiation 4

CD8+ T lymphocytes

T lymphocytes expressing the cluster differentiation 8


Cystic fibrosis


Cystic fibrosis transmembrane conductance regulator




Myelocytomotosis oncogene


Central nervous system


Cytosine-phosphate-guanine motifs


Cell-penetrating peptide


Calf timus DNA


3ß-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol


Delivery liposomal system


Dimyristoylphosphatidylethanolamine-polyethylene glycol5000


1,2-dimyristyloxypropyl-3-dimethyl-hydroxy ethyl ammonium bromide


Dimyristoyl 1,2-diacyl-3-trimethylammonium-propane


Dioctadecyl amino glycyl spermine




2,3 dioleyloxy-N-[2[sperminecarboxaminino]ethyl]-N,N-dimethyl-1-propanaminium trifluroacetate




Octadecenoyloxy[ethyl-2-heptadecenyl-3-hydroxyethyl] imidazolinium chloride






Epstein-Barr virus


Endothelial growth factor receptor


Egg yolk phosphatidylcholine




Egg yolk sphingomyelin


Folic acid


Folate receptor




Hemagglutinin subunit 2


Hepatitis B virus


Human epidermal growth factor receptor 2 proto-oncogene


Human immunodeficiency virus type 1


Human serum albumin


Herpes simplex virus-tymidine kinase


Human telomerase RNA component


Hemagglutinating virus of Japan


Half maximal inhibitory concentration
















LIM domain only 2




Monoclonal antibodies


Mannosylated liposomes


Modified formulation of antisense oligonucleotide targeting Raf-1


Murine double minute oncogene


Multifunctional envelope-type nanodevices


Macrophage inflammatory protein-1β




Messenger RNA


Nuclear factor kappa-light-chain-enhancer of activated B cells


Natural killer






Plasmid DNA


Polyethylene glycol


Proto-oncogene serine/threonine-protein kinase


RNA interference


Short hairpin RNA


Small interference RNA


Stabilized nucleic acid lipid particles


Splice-switching oligonucleotide


Simian vacuolating virus 40


Transferrin-associated lipoplexes


Transferrin receptor


Trojan Horse liposomes


Tumor infiltrating lymphocytes


Tumor necrosis factor-alpha


Mouse mammary adenocarcinoma


Ultradeformable cationic liposomes


Vascular endothelial growth factor



The authors wish to thank Pedro Carvalho for the artwork included in this chapter.


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Henrique Faneca
    • 1
  • Ana Luísa Cardoso
    • 1
  • Sara Trabulo
    • 1
  • Sónia Duarte
    • 1
  • Maria C. Pedroso de Lima
    • 1
    • 2
    Email author
  1. 1.Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbraPortugal
  2. 2.Department of Life SciencesUniversity of CoimbraCoimbraPortugal

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