Nano Science and Technology Institute
Nanotech 2008 Vol. 2
Nanotech 2008 Vol. 2
Nanotechnology 2008: Life Sciences, Medicine & Bio Materials - Technical Proceedings of the 2008 NSTI Nanotechnology Conference and Trade Show, Volume 2
 
Chapter 4: Drug & Gene Delivery Systems
 

Efficient siRNA Delivery by Secondary and Tertiary Amine Modified Polysaccharides

Authors:B. Ghosn, A. Singh, K. Roy
Affilation:The University of Texas at Austin, US
Pages:338 - 341
Keywords:chitosan, secondary amine, tertiary amine, pulmonary, intranasal, mucosal, endosomal escape
Abstract:As siRNA mediated therapy further develops, the need for biocompatible, effective delivery vectors, especially for mucosal delivery, is apparent. We report here a novel nanocarrier for siRNA delivery via targeted chemical modification of the polysaccharide chitosan. Although widely used in mucosal drug delivery applications, chitosan is limited by minimal solubility and buffering capacity at physiological pH as well as poor cell transfection efficacy compared to other polycations. We hypothesized that introduction of secondary and tertiary amines to the polymer backbone would enhance its solubility, endosomal escape capability and cytoplasmic siRNA dissociation, thus resulting in highly efficient gene silencing. Successful introduction of imidazole acetic acid (IAA) to chitosan was achieved using carbodiimide chemistry with up to 90% modification. Enhancement in buffering capacity and solubility were demonstrated even at high pH. As predicted, in vitro gene knockdown was greatly enhanced, nearly doubling in efficacy and matching commercially available transfection agents. Preliminary in vivo studies demonstrated effective gene knockdown in mice following intranasal administration of chitosan-IAA-siRNA nanocomplexes. GAPDH silencing was used as a model system and knockdown of up to 60 percent was achieved in the lung tissues. In summary, we have synthesized a biocompatible, mucoadhesive vector for enhanced in-vivo delivery of siRNA.
Efficient siRNA Delivery by Secondary and Tertiary Amine Modified PolysaccharidesView PDF of paper
ISBN:978-1-4200-8504-4
Pages:808
Hardcopy:$159.95
 
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