Ethanol enhanced in vivo gene delivery with non-ionic polymeric micelles inhalation

Yen Chin Chao, Shwu Fen Chang, Shao Chun Lu, Tzyh Chang Hwang, Wei Hsien Hsieh, Jiahorng Liaw

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Modifications of both carriers and host barriers have been investigated for efficient inhalation gene delivery to lung. Here we used a biocompatible, non-ionic poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) (PEO-PPO-PEO) polymeric micelles (PM) as a carrier and combined it with ethanol to enhance membrane penetration of delivered DNA. The inhalation delivery with six 100 μg doses of pCMV-Lac Z with PM co-formulated with 10%-40% ethanol to nude mice in 2 days at 8 h interval was performed. The β-galatosidase (β-Gal) activity was assessed using chlorophenol red-β-d galactopyranoside (CPRG) and X-gal staining for quantitative and qualitative analysis in tissues. The results showed that β-Gal activity was significantly increased by 38% in lung around bronchioles when inhalation with PM and 10% ethanol was given. The 10% ethanol also increased the intracellular apparent permeability by 42% in stomach and by 141% in intestine at 48 h after the first dosage of delivery. Also delivery of DNA encoding a functional human cystic fibrosis transmembrane protein (CFTR) using the same inhalation delivery method co-formulated with 10% ethanol, an increased expression of CFTR in lung was detected by immunostaining. We concluded that 10% ethanol co-formulated with the PM system could enhance inhaled gene delivery to airway and gastrointestinal (GI) tract.

Original languageEnglish
Pages (from-to)105-117
Number of pages13
JournalJournal of Controlled Release
Volume118
Issue number1
DOIs
Publication statusPublished - Mar 12 2007

Fingerprint

Micelles
Inhalation
Ethanol
Genes
Cystic Fibrosis
Lung
Bronchioles
DNA
Nude Mice
Intestines
Gastrointestinal Tract
Permeability
Stomach
Proteins
Staining and Labeling
Membranes

Keywords

  • CFTR
  • Ethanol
  • Gene
  • Inhalation
  • Polymeric micelles

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Ethanol enhanced in vivo gene delivery with non-ionic polymeric micelles inhalation. / Chao, Yen Chin; Chang, Shwu Fen; Lu, Shao Chun; Hwang, Tzyh Chang; Hsieh, Wei Hsien; Liaw, Jiahorng.

In: Journal of Controlled Release, Vol. 118, No. 1, 12.03.2007, p. 105-117.

Research output: Contribution to journalArticle

Chao, Yen Chin ; Chang, Shwu Fen ; Lu, Shao Chun ; Hwang, Tzyh Chang ; Hsieh, Wei Hsien ; Liaw, Jiahorng. / Ethanol enhanced in vivo gene delivery with non-ionic polymeric micelles inhalation. In: Journal of Controlled Release. 2007 ; Vol. 118, No. 1. pp. 105-117.
@article{34f973c2b6324f818ebc3fab1323c93b,
title = "Ethanol enhanced in vivo gene delivery with non-ionic polymeric micelles inhalation",
abstract = "Modifications of both carriers and host barriers have been investigated for efficient inhalation gene delivery to lung. Here we used a biocompatible, non-ionic poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) (PEO-PPO-PEO) polymeric micelles (PM) as a carrier and combined it with ethanol to enhance membrane penetration of delivered DNA. The inhalation delivery with six 100 μg doses of pCMV-Lac Z with PM co-formulated with 10{\%}-40{\%} ethanol to nude mice in 2 days at 8 h interval was performed. The β-galatosidase (β-Gal) activity was assessed using chlorophenol red-β-d galactopyranoside (CPRG) and X-gal staining for quantitative and qualitative analysis in tissues. The results showed that β-Gal activity was significantly increased by 38{\%} in lung around bronchioles when inhalation with PM and 10{\%} ethanol was given. The 10{\%} ethanol also increased the intracellular apparent permeability by 42{\%} in stomach and by 141{\%} in intestine at 48 h after the first dosage of delivery. Also delivery of DNA encoding a functional human cystic fibrosis transmembrane protein (CFTR) using the same inhalation delivery method co-formulated with 10{\%} ethanol, an increased expression of CFTR in lung was detected by immunostaining. We concluded that 10{\%} ethanol co-formulated with the PM system could enhance inhaled gene delivery to airway and gastrointestinal (GI) tract.",
keywords = "CFTR, Ethanol, Gene, Inhalation, Polymeric micelles",
author = "Chao, {Yen Chin} and Chang, {Shwu Fen} and Lu, {Shao Chun} and Hwang, {Tzyh Chang} and Hsieh, {Wei Hsien} and Jiahorng Liaw",
year = "2007",
month = "3",
day = "12",
doi = "10.1016/j.jconrel.2006.12.007",
language = "English",
volume = "118",
pages = "105--117",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Ethanol enhanced in vivo gene delivery with non-ionic polymeric micelles inhalation

AU - Chao, Yen Chin

AU - Chang, Shwu Fen

AU - Lu, Shao Chun

AU - Hwang, Tzyh Chang

AU - Hsieh, Wei Hsien

AU - Liaw, Jiahorng

PY - 2007/3/12

Y1 - 2007/3/12

N2 - Modifications of both carriers and host barriers have been investigated for efficient inhalation gene delivery to lung. Here we used a biocompatible, non-ionic poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) (PEO-PPO-PEO) polymeric micelles (PM) as a carrier and combined it with ethanol to enhance membrane penetration of delivered DNA. The inhalation delivery with six 100 μg doses of pCMV-Lac Z with PM co-formulated with 10%-40% ethanol to nude mice in 2 days at 8 h interval was performed. The β-galatosidase (β-Gal) activity was assessed using chlorophenol red-β-d galactopyranoside (CPRG) and X-gal staining for quantitative and qualitative analysis in tissues. The results showed that β-Gal activity was significantly increased by 38% in lung around bronchioles when inhalation with PM and 10% ethanol was given. The 10% ethanol also increased the intracellular apparent permeability by 42% in stomach and by 141% in intestine at 48 h after the first dosage of delivery. Also delivery of DNA encoding a functional human cystic fibrosis transmembrane protein (CFTR) using the same inhalation delivery method co-formulated with 10% ethanol, an increased expression of CFTR in lung was detected by immunostaining. We concluded that 10% ethanol co-formulated with the PM system could enhance inhaled gene delivery to airway and gastrointestinal (GI) tract.

AB - Modifications of both carriers and host barriers have been investigated for efficient inhalation gene delivery to lung. Here we used a biocompatible, non-ionic poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) (PEO-PPO-PEO) polymeric micelles (PM) as a carrier and combined it with ethanol to enhance membrane penetration of delivered DNA. The inhalation delivery with six 100 μg doses of pCMV-Lac Z with PM co-formulated with 10%-40% ethanol to nude mice in 2 days at 8 h interval was performed. The β-galatosidase (β-Gal) activity was assessed using chlorophenol red-β-d galactopyranoside (CPRG) and X-gal staining for quantitative and qualitative analysis in tissues. The results showed that β-Gal activity was significantly increased by 38% in lung around bronchioles when inhalation with PM and 10% ethanol was given. The 10% ethanol also increased the intracellular apparent permeability by 42% in stomach and by 141% in intestine at 48 h after the first dosage of delivery. Also delivery of DNA encoding a functional human cystic fibrosis transmembrane protein (CFTR) using the same inhalation delivery method co-formulated with 10% ethanol, an increased expression of CFTR in lung was detected by immunostaining. We concluded that 10% ethanol co-formulated with the PM system could enhance inhaled gene delivery to airway and gastrointestinal (GI) tract.

KW - CFTR

KW - Ethanol

KW - Gene

KW - Inhalation

KW - Polymeric micelles

UR - http://www.scopus.com/inward/record.url?scp=33847115752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847115752&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2006.12.007

DO - 10.1016/j.jconrel.2006.12.007

M3 - Article

C2 - 17258837

AN - SCOPUS:33847115752

VL - 118

SP - 105

EP - 117

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 1

ER -