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

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Book cover Drug Delivery Systems: Advanced Technologies Potentially Applicable in Personalised Treatment

Part of the book series: Advances in Predictive, Preventive and Personalised Medicine ((APPPM,volume 4))

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Abstract

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

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Abbreviations

5-FC:

5-fluorocytosine

AD:

Atopic dermatitis

Apo B:

Apolipoprotein B

ASO:

Antisense oligonucleotide

BBB:

Blood brain barrier

BCR-ABL:

Break cluster region-Abelson

CD:

Cytosine deaminase

CD4+ T lymphocytes:

T lymphocytes expressing the cluster differentiation 4

CD8+ T lymphocytes:

T lymphocytes expressing the cluster differentiation 8

CF:

Cystic fibrosis

CFTR:

Cystic fibrosis transmembrane conductance regulator

Chol:

Cholesterol

c-myc:

Myelocytomotosis oncogene

CNS:

Central nervous system

CpG:

Cytosine-phosphate-guanine motifs

CPP:

Cell-penetrating peptide

ctDNA:

Calf timus DNA

DC-Chol:

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

DLS:

Delivery liposomal system

DMPE-PEG5000 :

Dimyristoylphosphatidylethanolamine-polyethylene glycol5000

DMRIE:

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

DMTAP:

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

DOGS:

Dioctadecyl amino glycyl spermine

DOPE:

1,2-dioleoyl-sn-glycero-3-phosphoethanolamine

DOSPA:

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

DOTAP:

1,2-dioleoyl-3-trimethylammonium-propane

DOTIM:

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

DOTMA:

2,3-bis[oleyl]oxipropyltrimethylammoniumchloride

DSPE:

1,2-distearoyl-sn-glycero-3-phosphoethanolamine

EBV:

Epstein-Barr virus

EGFR:

Endothelial growth factor receptor

ePC:

Egg yolk phosphatidylcholine

EPOPC:

1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine

eSph:

Egg yolk sphingomyelin

FA:

Folic acid

FR:

Folate receptor

GCV:

Ganciclovir

HA2:

Hemagglutinin subunit 2

HBV:

Hepatitis B virus

HER-2/neu:

Human epidermal growth factor receptor 2 proto-oncogene

HIV-1:

Human immunodeficiency virus type 1

HSA:

Human serum albumin

HSV-tk:

Herpes simplex virus-tymidine kinase

hTR:

Human telomerase RNA component

HVJ:

Hemagglutinating virus of Japan

IC50 :

Half maximal inhibitory concentration

IFN-α:

Interferon-alpha

IFN-β:

Interferon-beta

IFN-γ:

Interferon-gamma

IL-12:

Interleukin-12

IL-13:

Interleukin-13

IL-18:

Interleukin-18

IL-4:

Interleukin-4

LMO2:

LIM domain only 2

LPS:

Lipopolysaccharide

MAbs:

Monoclonal antibodies

Man-liposomes:

Mannosylated liposomes

md-LErafAON:

Modified formulation of antisense oligonucleotide targeting Raf-1

MDM2:

Murine double minute oncogene

MEND:

Multifunctional envelope-type nanodevices

MIP-1β:

Macrophage inflammatory protein-1β

miRNA:

microRNA

mRNA:

Messenger RNA

NFκB:

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

NK:

Natural killer

ON:

Oligonucleotide

PC:

Phosphatidylcholine

pDNA:

Plasmid DNA

PEG:

Polyethylene glycol

Raf-1:

Proto-oncogene serine/threonine-protein kinase

RNAi:

RNA interference

shRNA:

Short hairpin RNA

siRNA:

Small interference RNA

SNALPs:

Stabilized nucleic acid lipid particles

SSO:

Splice-switching oligonucleotide

SV40:

Simian vacuolating virus 40

Tf-lipoplexes:

Transferrin-associated lipoplexes

TfR:

Transferrin receptor

THL:

Trojan Horse liposomes

TIL:

Tumor infiltrating lymphocytes

TNF-α:

Tumor necrosis factor-alpha

TSA:

Mouse mammary adenocarcinoma

UCL:

Ultradeformable cationic liposomes

VEGF:

Vascular endothelial growth factor

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Acknowledgments

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

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Authors and Affiliations

  1. Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Henrique Faneca, Ana Luísa Cardoso, Sara Trabulo, Sónia Duarte & Maria C. Pedroso de Lima

  2. Department of Life Sciences, University of Coimbra, Apartado 3046, 3001-401, Coimbra, Portugal

    Maria C. Pedroso de Lima

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  1. Henrique Faneca
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  2. Ana Luísa Cardoso
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  3. Sara Trabulo
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  4. Sónia Duarte
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  5. Maria C. Pedroso de Lima
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Correspondence to Maria C. Pedroso de Lima .

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  1. , Chemical Engineering, University of Coimbra, Rua Silvio Lima, Coimbra, 3030 790, Portugal

    Jorge Coelho

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Faneca, H., Cardoso, A.L., Trabulo, S., Duarte, S., de Lima, M.C.P. (2013). Cationic Liposome-Based Systems for Nucleic Acid Delivery: From the Formulation Development to Therapeutic Applications. In: Coelho, J. (eds) Drug Delivery Systems: Advanced Technologies Potentially Applicable in Personalised Treatment. Advances in Predictive, Preventive and Personalised Medicine, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6010-3_6

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