Premium
Oral gene delivery: Design of polymeric carrier systems shielding toward intestinal enzymatic attack
Author(s) -
Martien Ronny,
Loretz Brigitta,
Schnürch A. B.
Publication year - 2006
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20521
Subject(s) - chitosan , chemistry , gene delivery , zeta potential , nanoparticle , transfection , conjugate , polyelectrolyte , polymer , biophysics , nuclear chemistry , nanotechnology , biochemistry , organic chemistry , materials science , gene , mathematical analysis , mathematics , biology
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 biopolymers@wiley.com