Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle

Chien Wen Chang, Donghoon Choi, Won Jong Kim, James W. Yockman, Lane V. Christensen, Yong Hee Kim, Sung Wan Kim

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Naked plasmid DNA (pDNA)-based gene therapy has low delivery efficiency, and consequently, low therapeutic effect. We present a biodegradable nonionic triblock copolymer, PEG13-PLGA10-PEG13, to enhance gene delivery efficiency in skeletal muscle. Effects of PEG13-PLGA10-PEG13 on physicochemical properties of pDNA were evaluated by atomic force microscopy (AFM) imaging, gel electrophoresis and zeta-potential analysis. AFM imaging suggested a slightly compacted structure of pDNA when it was mixed with the polymer, while zeta-potential measurement indicated an increased surface potential of negatively charged pDNA. PEG13-PLGA10-PEG13 showed a relatively lower toxicity compared to Pluronic P85 in a skeletal muscle cell line. The luciferase expression of pDNA delivered in 0.25% polymer solution was up to three orders of magnitude more than branched polyethylenimine (bPEI(25 k))/pDNA and three times more than that of naked pDNA five days after intramuscular administration. This in vivo gene delivery enhancement was also observed displaying a two-fold higher expression of human vascular endothelial growth factor (VEGF). Based on fluorescence labeled pDNA distribution, it is speculated that the greater diffusivity of PEG13-PLGA10-PEG13/pDNA compared to bPEI(25 k)/pDNA accounts for better transfection efficiency in vivo. To summarize, combining PEG13-PLGA10-PEG13 with pDNA possesses the potential to improve gene delivery efficiency in skeletal muscle.

Original languageEnglish
Pages (from-to)245-253
Number of pages9
JournalJournal of Controlled Release
Volume118
Issue number2
DOIs
Publication statusPublished - 2007 Apr 2

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Skeletal Muscle
Plasmids
DNA
Genes
Atomic Force Microscopy
Polymers
polyethylene glycol-poly(lactic-co-glycolic acid)-polyethylene glycol
poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
Polyethyleneimine
Poloxamer
Therapeutic Uses
Luciferases
Genetic Therapy
Muscle Cells
Transfection
Electrophoresis
Fluorescence
Gels
Cell Line

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Chang, Chien Wen ; Choi, Donghoon ; Kim, Won Jong ; Yockman, James W. ; Christensen, Lane V. ; Kim, Yong Hee ; Kim, Sung Wan. / Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle. In: Journal of Controlled Release. 2007 ; Vol. 118, No. 2. pp. 245-253.
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abstract = "Naked plasmid DNA (pDNA)-based gene therapy has low delivery efficiency, and consequently, low therapeutic effect. We present a biodegradable nonionic triblock copolymer, PEG13-PLGA10-PEG13, to enhance gene delivery efficiency in skeletal muscle. Effects of PEG13-PLGA10-PEG13 on physicochemical properties of pDNA were evaluated by atomic force microscopy (AFM) imaging, gel electrophoresis and zeta-potential analysis. AFM imaging suggested a slightly compacted structure of pDNA when it was mixed with the polymer, while zeta-potential measurement indicated an increased surface potential of negatively charged pDNA. PEG13-PLGA10-PEG13 showed a relatively lower toxicity compared to Pluronic P85 in a skeletal muscle cell line. The luciferase expression of pDNA delivered in 0.25{\%} polymer solution was up to three orders of magnitude more than branched polyethylenimine (bPEI(25 k))/pDNA and three times more than that of naked pDNA five days after intramuscular administration. This in vivo gene delivery enhancement was also observed displaying a two-fold higher expression of human vascular endothelial growth factor (VEGF). Based on fluorescence labeled pDNA distribution, it is speculated that the greater diffusivity of PEG13-PLGA10-PEG13/pDNA compared to bPEI(25 k)/pDNA accounts for better transfection efficiency in vivo. To summarize, combining PEG13-PLGA10-PEG13 with pDNA possesses the potential to improve gene delivery efficiency in skeletal muscle.",
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Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle. / Chang, Chien Wen; Choi, Donghoon; Kim, Won Jong; Yockman, James W.; Christensen, Lane V.; Kim, Yong Hee; Kim, Sung Wan.

In: Journal of Controlled Release, Vol. 118, No. 2, 02.04.2007, p. 245-253.

Research output: Contribution to journalArticle

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