Oral gene delivery: Design of polymeric carrier systems shielding toward intestinal enzymatic attack
✍ Scribed by Ronny Martien; Brigitta Loretz; A. B. Schnürch
- Book ID
- 102760748
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 2006
- Tongue
- English
- Weight
- 598 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
Abstract
The gastrointestinal tract poses a variety of morphological and physiological barriers to the expression of target genes. The aim of this study was to evaluate the stability of cationic polymer/pDNA nanoparticles toward salts and enzymes of the intestinal fluid. Within this study, a chitosan–enzyme inhibitor conjugate has been generated and characterized. Based on this conjugate, nanoparticles with pDNA were generated to enhance transfection rate in oral gene delivery. The enzyme inhibitor aurintricarboxylic acid (ATA) was covalently bound to chitosan to improve the enzymatic stability of nanoparticles formed with this polymer and pDNA. Chitosan–ATA/pDNA nanoparticles showed a size of 98.5 ± 26 nm and a zeta potential of −13.26 ± 0.24 mV (n = 3–4). Stability studies with salt solution, lysozyme, DNase, and freshly collected porcine intestinal fluid showed that chitosan–ATA/pDNA nanoparticles are significantly (p < 0.05) more stable than unmodified chitosan/pDNA nanoparticles. Apart from improved stability, chitosan–ATA/pDNA nanoparticles showed a 2.6‐fold higher transfection rate than chitosan/pDNA nanoparticles in the Caco‐2 cell line, thus creating a promising carrier for orally administered therapeutic genes. © 2006 Wiley Periodicals, Inc. Biopolymers 83:327–336, 2006
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]