FRET-based dual-emission and pH-responsive nanocarriers for enhanced delivery of protein across intestinal epithelial cell barrier

Kun Ying Lu, Cheng Wei Lin, Chun Hua Hsu, Yi Cheng Ho, Er-Tuan Chuang, Hsing Wen Sung, Fwu Long Mi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The oral route is a convenient and commonly employed way for drug delivery. However, therapeutic proteins have poor bioavailability upon oral administration due to the impermeable barrier from intestinal epithelial tight junction (TJ). Moreover, the pH of the small intestine varies among different regions of the intestinal tract where digestion and absorption occur at different levels. In this study, a tunable dual-emitting and pH-responsive nanocarrier that can alter the fluorescent color and emission intensity in response to pH changes and can trigger the opening of intestinal epithelial TJ at different levels were developed from chitosan-N-arginine and poly(γ-glutamic acid)-taurine conjugates. As pH increased from 6.0 to 8.0, the binding affinity of the oppositely charged polyions decreased, whereas the ratio of the intensity of the donor-to-acceptor emission intensity (ID/IA) increased by 27-fold. The fluorescent and pH-responsive nanocarrier was able to monitor the pH change of intestinal environment and to control the release of an anti-angiogenic protein in response to the pH gradient. The nanocarrier triggered the opening of intestinal epithelial TJ and consequently enhanced the permeation of the released protein through the intestinal epithelial barrier model (Caco-2 cell monolayer) to inhibit tube formation of human umbilical vein endothelial cells.

Original languageEnglish
Pages (from-to)18275-18289
Number of pages15
JournalACS Applied Materials and Interfaces
Volume6
Issue number20
DOIs
Publication statusPublished - Oct 22 2014

Fingerprint

Angiogenic Proteins
Epithelial Cells
Proteins
Tight Junctions
Taurine
Endothelial cells
Chitosan
Drug delivery
Permeation
Arginine
Glutamic Acid
Monolayers
Color
Proton-Motive Force
Caco-2 Cells
Acids
Human Umbilical Vein Endothelial Cells
Biological Availability
Small Intestine
Oral Administration

Keywords

  • chitosan
  • drug delivery
  • pH-responsive
  • protein release

ASJC Scopus subject areas

  • Materials Science(all)
  • Medicine(all)

Cite this

FRET-based dual-emission and pH-responsive nanocarriers for enhanced delivery of protein across intestinal epithelial cell barrier. / Lu, Kun Ying; Lin, Cheng Wei; Hsu, Chun Hua; Ho, Yi Cheng; Chuang, Er-Tuan; Sung, Hsing Wen; Mi, Fwu Long.

In: ACS Applied Materials and Interfaces, Vol. 6, No. 20, 22.10.2014, p. 18275-18289.

Research output: Contribution to journalArticle

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