PEG-b-PPA/DNA micelles improve transgene expression in rat liver through intrabiliary infusion

Xuan Jiang; Hui Dai; Chyan Ying Ke; Xiao Mo; Michael S. Torbenson; Zhiping Li; Hai Quan Mao

doi:10.1016/j.jconrel.2007.06.014

PEG-b-PPA/DNA micelles improve transgene expression in rat liver through intrabiliary infusion

Xuan Jiang, Hui Dai, Chyan Ying Ke, Xiao Mo, Michael S. Torbenson, Zhiping Li, Hai Quan Mao

Laboratory Medicine and Pathology

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

36 Scopus citations

Abstract

We have developed a new block copolymer gene carrier that comprises of a polyethylene glycol segment and a degradable cationic polyphosphoramidate (PPA) segment. This PEG-b-PPA copolymer carrier formed micelles upon condensation with plasmid DNA in aqueous solution. PEG-b-PPA/DNA micelles exhibited uniform and reduced particle size ranging from 80 to 100 nm and lowered surface charge, compared with complexes of DNA with the corresponding cationic PPA carrier. PEG-b-PPA/DNA micelles maintained similar transfection efficiency as PPA/DNA complexes, which was comparable to that of PEI/DNA complexes in HepG2 cells, but yielded about 16-fold lower transgene expression in primary rat hepatocytes than PPA/DNA complexes. Following bile duct infusion in Wistar rats, PEG-b-PPA/DNA micelles mediated 4-fold higher and more uniform gene expression in the liver than PPA/DNA complexes. Liver function tests and histopathological examination indicated that PEG-b-PPA/DNA micelles showed low toxicity and good biocompatibility in the liver. This study demonstrated the potential of PEG-b-PPA/DNA micelles as an efficient carrier for liver-targeted gene delivery.

Original language	English (US)
Pages (from-to)	297-304
Number of pages	8
Journal	Journal of Controlled Release
Volume	122
Issue number	3
DOIs	https://doi.org/10.1016/j.jconrel.2007.06.014
State	Published - Oct 8 2007

Keywords

Block copolymer
Gene delivery
Intrabiliary infusion
Liver-targeted
Polymeric micelles
Polyphosphoramidate

ASJC Scopus subject areas

Pharmaceutical Science

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10.1016/j.jconrel.2007.06.014

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title = "PEG-b-PPA/DNA micelles improve transgene expression in rat liver through intrabiliary infusion",

abstract = "We have developed a new block copolymer gene carrier that comprises of a polyethylene glycol segment and a degradable cationic polyphosphoramidate (PPA) segment. This PEG-b-PPA copolymer carrier formed micelles upon condensation with plasmid DNA in aqueous solution. PEG-b-PPA/DNA micelles exhibited uniform and reduced particle size ranging from 80 to 100 nm and lowered surface charge, compared with complexes of DNA with the corresponding cationic PPA carrier. PEG-b-PPA/DNA micelles maintained similar transfection efficiency as PPA/DNA complexes, which was comparable to that of PEI/DNA complexes in HepG2 cells, but yielded about 16-fold lower transgene expression in primary rat hepatocytes than PPA/DNA complexes. Following bile duct infusion in Wistar rats, PEG-b-PPA/DNA micelles mediated 4-fold higher and more uniform gene expression in the liver than PPA/DNA complexes. Liver function tests and histopathological examination indicated that PEG-b-PPA/DNA micelles showed low toxicity and good biocompatibility in the liver. This study demonstrated the potential of PEG-b-PPA/DNA micelles as an efficient carrier for liver-targeted gene delivery.",

keywords = "Block copolymer, Gene delivery, Intrabiliary infusion, Liver-targeted, Polymeric micelles, Polyphosphoramidate",

author = "Xuan Jiang and Hui Dai and Ke, {Chyan Ying} and Xiao Mo and Torbenson, {Michael S.} and Zhiping Li and Mao, {Hai Quan}",

note = "Funding Information: This study is supported in part by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (DK068399, H. Q. Mao) and New Faculty Startup Fund from Whiting School of Engineering and Whitaker Biomedical Engineering Institute, Johns Hopkins University.",

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doi = "10.1016/j.jconrel.2007.06.014",

language = "English (US)",

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T1 - PEG-b-PPA/DNA micelles improve transgene expression in rat liver through intrabiliary infusion

AU - Jiang, Xuan

AU - Dai, Hui

AU - Ke, Chyan Ying

AU - Mo, Xiao

AU - Torbenson, Michael S.

AU - Li, Zhiping

AU - Mao, Hai Quan

N1 - Funding Information: This study is supported in part by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (DK068399, H. Q. Mao) and New Faculty Startup Fund from Whiting School of Engineering and Whitaker Biomedical Engineering Institute, Johns Hopkins University.

PY - 2007/10/8

Y1 - 2007/10/8

N2 - We have developed a new block copolymer gene carrier that comprises of a polyethylene glycol segment and a degradable cationic polyphosphoramidate (PPA) segment. This PEG-b-PPA copolymer carrier formed micelles upon condensation with plasmid DNA in aqueous solution. PEG-b-PPA/DNA micelles exhibited uniform and reduced particle size ranging from 80 to 100 nm and lowered surface charge, compared with complexes of DNA with the corresponding cationic PPA carrier. PEG-b-PPA/DNA micelles maintained similar transfection efficiency as PPA/DNA complexes, which was comparable to that of PEI/DNA complexes in HepG2 cells, but yielded about 16-fold lower transgene expression in primary rat hepatocytes than PPA/DNA complexes. Following bile duct infusion in Wistar rats, PEG-b-PPA/DNA micelles mediated 4-fold higher and more uniform gene expression in the liver than PPA/DNA complexes. Liver function tests and histopathological examination indicated that PEG-b-PPA/DNA micelles showed low toxicity and good biocompatibility in the liver. This study demonstrated the potential of PEG-b-PPA/DNA micelles as an efficient carrier for liver-targeted gene delivery.

AB - We have developed a new block copolymer gene carrier that comprises of a polyethylene glycol segment and a degradable cationic polyphosphoramidate (PPA) segment. This PEG-b-PPA copolymer carrier formed micelles upon condensation with plasmid DNA in aqueous solution. PEG-b-PPA/DNA micelles exhibited uniform and reduced particle size ranging from 80 to 100 nm and lowered surface charge, compared with complexes of DNA with the corresponding cationic PPA carrier. PEG-b-PPA/DNA micelles maintained similar transfection efficiency as PPA/DNA complexes, which was comparable to that of PEI/DNA complexes in HepG2 cells, but yielded about 16-fold lower transgene expression in primary rat hepatocytes than PPA/DNA complexes. Following bile duct infusion in Wistar rats, PEG-b-PPA/DNA micelles mediated 4-fold higher and more uniform gene expression in the liver than PPA/DNA complexes. Liver function tests and histopathological examination indicated that PEG-b-PPA/DNA micelles showed low toxicity and good biocompatibility in the liver. This study demonstrated the potential of PEG-b-PPA/DNA micelles as an efficient carrier for liver-targeted gene delivery.

KW - Block copolymer

KW - Gene delivery

KW - Intrabiliary infusion

KW - Liver-targeted

KW - Polymeric micelles

KW - Polyphosphoramidate

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PEG-b-PPA/DNA micelles improve transgene expression in rat liver through intrabiliary infusion

Abstract

Keywords

ASJC Scopus subject areas

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