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

doi:10.1016/j.jconrel.2006.11.025

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

Department of Internal Medicine

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

63 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 language	English
Pages (from-to)	245-253
Number of pages	9
Journal	Journal of Controlled Release
Volume	118
Issue number	2
DOIs	https://doi.org/10.1016/j.jconrel.2006.11.025
Publication status	Published - 2007 Apr 2

Bibliographical note

Funding Information:
This work was supported by NIH grant HL 65477. Thanks to Jui-Mei Hsu for her technical assistance with our histology work. Thanks to Loren Rieth and Andras Pungor for their technical assistance on AFM imaging. Thanks to MacroMed for providing the PEG 13 –PLGA 10 –PEG 13 polymer.

All Science Journal Classification (ASJC) codes

Pharmaceutical Science

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10.1016/j.jconrel.2006.11.025

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@article{66848906aa314df28f2e73505abddb43,

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

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.",

author = "Chang, {Chien Wen} and Donghoon Choi and Kim, {Won Jong} and Yockman, {James W.} and Christensen, {Lane V.} and Kim, {Yong Hee} and Kim, {Sung Wan}",

note = "Funding Information: This work was supported by NIH grant HL 65477. Thanks to Jui-Mei Hsu for her technical assistance with our histology work. Thanks to Loren Rieth and Andras Pungor for their technical assistance on AFM imaging. Thanks to MacroMed for providing the PEG 13 –PLGA 10 –PEG 13 polymer.",

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doi = "10.1016/j.jconrel.2006.11.025",

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T1 - Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle

AU - Chang, Chien Wen

AU - Choi, Donghoon

AU - Kim, Won Jong

AU - Yockman, James W.

AU - Christensen, Lane V.

AU - Kim, Yong Hee

AU - Kim, Sung Wan

N1 - Funding Information: This work was supported by NIH grant HL 65477. Thanks to Jui-Mei Hsu for her technical assistance with our histology work. Thanks to Loren Rieth and Andras Pungor for their technical assistance on AFM imaging. Thanks to MacroMed for providing the PEG 13 –PLGA 10 –PEG 13 polymer.

PY - 2007/4/2

Y1 - 2007/4/2

N2 - 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.

AB - 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

Abstract

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