Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle
- Authors
- Chang, Chien Wen; Choi, Donghoon; Kim, Won Jong; Yockman, James W.; Christensen, Lane V.; Kim, Yong Hee; Kim, Sung Wan
- Issue Date
- Apr-2007
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- gene therapy; PEG-PLGA-PEG; skeletal muscle; plasmid DNA; VEGF; biodegradable
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.118, no.2, pp.245 - 253
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 118
- Number
- 2
- Start Page
- 245
- End Page
- 253
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/180284
- DOI
- 10.1016/j.jconrel.2006.11.025
- ISSN
- 0168-3659
- Abstract
- Naked plasmid DNA (pDNA)-based gene therapy has low delivery efficiency, and consequently, low therapeutic effect. We present a biodegradable nonionic triblock copolymer, PEG(13)-PLGA(10)-PEG(13), to enhance gene delivery efficiency in skeletal muscle. Effects of PEG(13)PLGA(10)-PEG(13) 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. PEG(13)-PLGA(10)-PEG(13) 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 PEG(13)-PLGA(10)-PEG(13)/pDNA compared to bPET(25 k)/pDNA accounts for better transfection efficiency in vivo. To summarize, combining PEG(13)-PLGA(10)-PEG(13) with pDNA possesses the potential to improve gene delivery efficiency in skeletal muscle.
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