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

Keywords

  • CFTR
  • Ethanol
  • Gene
  • Inhalation
  • Polymeric micelles

ASJC Scopus subject areas

  • Pharmaceutical Science

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