Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA

Different viral and non-viral vectors have been designed to allow the delivery of nucleic acids in gene therapy. In general, non-viral vectors have been associated with increased safety for <i>in vivo</i> use; however, issues regarding their efficacy, toxicity and stability continue to d...

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Autores principales: Temprana, Carlos Facundo, Prieto, María Jimena, Igartúa, Daniela Edith, Femia, A. Lis, Amor, M. Silvia, Alonso, Silvia del Valle
Formato: Articulo
Lenguaje:Inglés
Publicado: 2017
Materias:
Ciencias Exactas
Diacetylenic lipids
plasmid DNA
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/87154
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-87154
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Diacetylenic lipids
plasmid DNA
spellingShingle Ciencias Exactas
Diacetylenic lipids
plasmid DNA
Temprana, Carlos Facundo
Prieto, María Jimena
Igartúa, Daniela Edith
Femia, A. Lis
Amor, M. Silvia
Alonso, Silvia del Valle
Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA
topic_facet Ciencias Exactas
Diacetylenic lipids
plasmid DNA
description Different viral and non-viral vectors have been designed to allow the delivery of nucleic acids in gene therapy. In general, non-viral vectors have been associated with increased safety for <i>in vivo</i> use; however, issues regarding their efficacy, toxicity and stability continue to drive further research. Thus, the aim of this study was to evaluate the potential use of the polymerizable diacetylenic lipid 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC<sub>8,9</sub>PC) as a strategy to formulate stable cationic lipopolymers in the delivery and protection of plasmid DNA. Cationic lipopolymers were prepared following two different methodologies by using DC<sub>8,9</sub>PC, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and the cationic lipids (CL) 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), stearylamine (SA), and myristoylcholine chloride (MCL), in a molar ratio of 1:1:0.2 (DMPC:DC<sub>8,9</sub>PC:CL). The copolymerization methodology allowed obtaining cationic lipopolymers which were smaller in size than those obtained by the cationic addition methodology although both techniques presented high size stability over a 166-day incubation period at 4C. Cationic lipopolymers containing DOTAP or MCL were more efficient in complexing DNA than those containing SA. Moreover, lipopolymers containing DOTAP were found to form highly stable complexes with DNA, able to resist serum DNAses degradation. Furthermore, neither of the cationic lipopolymers (with or without DNA) induced red blood cell hemolysis, although metabolic activity determined on the L-929 and Vero cell lines was found to be dependent on the cell line, the formulation and the presence of DNA. The high stability and DNA protection capacity as well as the reduced toxicity determined for the cationic lipopolymer containing DOTAP highlight the potential advantage of using lipopolymers when designing novel nonviral carrier systems for use in <i>in vivo</i> gene therapy. Thus, this work represents the first steps toward developing a cationic lipopolymer-based gene delivery system using polymerizable and cationic lipids.
format Articulo
Articulo
author Temprana, Carlos Facundo
Prieto, María Jimena
Igartúa, Daniela Edith
Femia, A. Lis
Amor, M. Silvia
Alonso, Silvia del Valle
author_facet Temprana, Carlos Facundo
Prieto, María Jimena
Igartúa, Daniela Edith
Femia, A. Lis
Amor, M. Silvia
Alonso, Silvia del Valle
author_sort Temprana, Carlos Facundo
title Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA
title_short Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA
title_full Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA
title_fullStr Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA
title_full_unstemmed Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA
title_sort diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid dna
publishDate 2017
url http://sedici.unlp.edu.ar/handle/10915/87154
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