Intracellular delivery of VEGF165 encoding gene therapeutic using trifunctional copolymers of ethylene oxide and propylene oxide

Oksana Bondaruk; Vesta Shevchenko; Alina Martynova; Diana Salakhieva; Irina Savina; Yurii Shtyrlina; Timur I. Abdullin

doi:10.1016/j.eurpolymj.2015.03.042

Intracellular delivery of VEGF165 encoding gene therapeutic using trifunctional copolymers of ethylene oxide and propylene oxide

Oksana Bondaruk, Vesta Shevchenko, Alina Martynova, Diana Salakhieva, Irina Savina, Yurii Shtyrlina, Timur I. Abdullin

Research output: Contribution to journal › Article › peer-review

Abstract

New type of copolymers of propylene oxide and ethylene oxide was assessed for promoting delivery of plasmid DNA based gene therapeutics. Lipid-like trifunctional copolymers (TFCs), with both random or diblock structures and relatively low hydrophilic-lipophilic balance, were studied and compared with linear Pluronic™ L61. Structure-dependent relationships for micelle-forming, cytotoxic and hemolytic properties of these copolymers were revealed. The TFC with the mean number of propylene oxide and ethylene oxide units of 83.5 and 24.2, respectively, exhibited relatively low adverse effects in vitro. The latter TFC interacted with plasmid DNA-polyethyleneimine complexes and improved their intracellular delivery. Furthermore, this TFC efficiently promoted the transfection of dermal fibroblasts with VEGF165-encoding Neovasculgen® plasmid DNA, which has been clinically used for the therapeutic angiogenesis. Our findings demonstrated for the first time that TFCs are promising for the polymer-mediated delivery of gene therapeutics

Original language	English
Pages (from-to)	680-686
Number of pages	7
Journal	European Polymer Journal
Volume	68
DOIs	https://doi.org/10.1016/j.eurpolymj.2015.03.042
Publication status	Published - 26 Mar 2015

Bibliographical note

Keywords

Trifunctional copolymers of propylene oxide and ethylene oxide
Pluronics
Polymer-mediated gene therapy
Plasmid DNA
Neovasculgen
VEGF165

Access to Document

10.1016/j.eurpolymj.2015.03.042Licence: Unspecified

Manuscript DNA delivery revised.pdfAccepted author manuscript, 319 KBLicence: CC BY-NC-ND

Irina Savina
- I.N.Savinabrighton.acuk
Person: Academic

Cite this

@article{ba00f88f89c64274961a7029da7db984,

title = "Intracellular delivery of VEGF165 encoding gene therapeutic using trifunctional copolymers of ethylene oxide and propylene oxide",

abstract = "New type of copolymers of propylene oxide and ethylene oxide was assessed for promoting delivery of plasmid DNA based gene therapeutics. Lipid-like trifunctional copolymers (TFCs), with both random or diblock structures and relatively low hydrophilic-lipophilic balance, were studied and compared with linear Pluronic{\texttrademark} L61. Structure-dependent relationships for micelle-forming, cytotoxic and hemolytic properties of these copolymers were revealed. The TFC with the mean number of propylene oxide and ethylene oxide units of 83.5 and 24.2, respectively, exhibited relatively low adverse effects in vitro. The latter TFC interacted with plasmid DNA-polyethyleneimine complexes and improved their intracellular delivery. Furthermore, this TFC efficiently promoted the transfection of dermal fibroblasts with VEGF165-encoding Neovasculgen{\textregistered} plasmid DNA, which has been clinically used for the therapeutic angiogenesis. Our findings demonstrated for the first time that TFCs are promising for the polymer-mediated delivery of gene therapeutics",

keywords = "Trifunctional copolymers of propylene oxide and ethylene oxide, Pluronics, Polymer-mediated gene therapy, Plasmid DNA, Neovasculgen, VEGF165",

author = "Oksana Bondaruk and Vesta Shevchenko and Alina Martynova and Diana Salakhieva and Irina Savina and Yurii Shtyrlina and Abdullin, {Timur I.}",

note = "{\textcopyright} 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/",

year = "2015",

month = mar,

day = "26",

doi = "10.1016/j.eurpolymj.2015.03.042",

language = "English",

volume = "68",

pages = "680--686",

journal = "European Polymer Journal",

issn = "0014-3057",

}

TY - JOUR

T1 - Intracellular delivery of VEGF165 encoding gene therapeutic using trifunctional copolymers of ethylene oxide and propylene oxide

AU - Bondaruk, Oksana

AU - Shevchenko, Vesta

AU - Martynova, Alina

AU - Salakhieva, Diana

AU - Savina, Irina

AU - Shtyrlina, Yurii

AU - Abdullin, Timur I.

PY - 2015/3/26

Y1 - 2015/3/26

N2 - New type of copolymers of propylene oxide and ethylene oxide was assessed for promoting delivery of plasmid DNA based gene therapeutics. Lipid-like trifunctional copolymers (TFCs), with both random or diblock structures and relatively low hydrophilic-lipophilic balance, were studied and compared with linear Pluronic™ L61. Structure-dependent relationships for micelle-forming, cytotoxic and hemolytic properties of these copolymers were revealed. The TFC with the mean number of propylene oxide and ethylene oxide units of 83.5 and 24.2, respectively, exhibited relatively low adverse effects in vitro. The latter TFC interacted with plasmid DNA-polyethyleneimine complexes and improved their intracellular delivery. Furthermore, this TFC efficiently promoted the transfection of dermal fibroblasts with VEGF165-encoding Neovasculgen® plasmid DNA, which has been clinically used for the therapeutic angiogenesis. Our findings demonstrated for the first time that TFCs are promising for the polymer-mediated delivery of gene therapeutics

AB - New type of copolymers of propylene oxide and ethylene oxide was assessed for promoting delivery of plasmid DNA based gene therapeutics. Lipid-like trifunctional copolymers (TFCs), with both random or diblock structures and relatively low hydrophilic-lipophilic balance, were studied and compared with linear Pluronic™ L61. Structure-dependent relationships for micelle-forming, cytotoxic and hemolytic properties of these copolymers were revealed. The TFC with the mean number of propylene oxide and ethylene oxide units of 83.5 and 24.2, respectively, exhibited relatively low adverse effects in vitro. The latter TFC interacted with plasmid DNA-polyethyleneimine complexes and improved their intracellular delivery. Furthermore, this TFC efficiently promoted the transfection of dermal fibroblasts with VEGF165-encoding Neovasculgen® plasmid DNA, which has been clinically used for the therapeutic angiogenesis. Our findings demonstrated for the first time that TFCs are promising for the polymer-mediated delivery of gene therapeutics

KW - Trifunctional copolymers of propylene oxide and ethylene oxide

KW - Pluronics

KW - Polymer-mediated gene therapy

KW - Plasmid DNA

KW - Neovasculgen

KW - VEGF165

U2 - 10.1016/j.eurpolymj.2015.03.042

DO - 10.1016/j.eurpolymj.2015.03.042

M3 - Article

SN - 0014-3057

VL - 68

SP - 680

EP - 686

JO - European Polymer Journal

JF - European Polymer Journal

ER -

Intracellular delivery of VEGF165 encoding gene therapeutic using trifunctional copolymers of ethylene oxide and propylene oxide

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Profiles

Irina Savina

Cite this