Christelle Zandanel1, Magali Noiray1, Christine Vauthier2. 1. Institut Galien Paris-Sud, CNRS UMR 8612, Univ Paris-Sud, Faculté de Pharmacie, 5 rue J.B. Clément, 92296, Châtenay-Malabry Cedex, France. 2. Institut Galien Paris-Sud, CNRS UMR 8612, Univ Paris-Sud, Faculté de Pharmacie, 5 rue J.B. Clément, 92296, Châtenay-Malabry Cedex, France. christine.vauthier@u-psud.fr.
Abstract
PURPOSE: The work aimed to compare quality of a siRNA carrier prepared with chitosan of two different sources having similar degree of deacetylation and molecular weights. Differences were analyzed from thermodynamic characteristics of interactions with siRNA. METHODS: The siRNA carrier (chitosan-coated poly(isobutylcyanoacrylate) nanoparticles) was prepared with home-prepared, CSLab, and commercial, CSCom, chitosans. Chitosan counterion was identified and chitosans CSCommod1 and CSCommod2 were obtained from CSCom exchanging counterion with that found on CSLab. Carrier quality was checked considering the size, zeta potential and siRNA association capacity by gel electrophoresis. Thermodynamic parameters of interactions between siRNA and chitosans in solution or immobilized at the carrier surface were determined by isothermal titration calorimetry (ITC). RESULTS: CSLab and CSCommod2 having a high content of acetate counterion associated better siRNA than CSCom and CSCommod1 which counterion included mainly chloride. ITC measurements indicated that siRNA interactions with chitosan and the siRNA carrier were driven by entropic phenomena including dehydration, but thermodynamic parameters of interactions clearly differed according to the nature of the counterion of chitosan. The influence of chitosan counterions was interpreted considering their different lyotropic character. CONCLUSION: Association of siRNA with our siRNA carrier was influenced by the nature of counterions associated with chitosan. Driven by entropic phenomena including dehydration, interactions were favored by acetate counterion. Although more work would be needed to decipher the influence of the counterion of chitosan during association with siRNA, it was pointed out as a new critical attribute of chitosan to consider while formulating siRNA carrier with this polysaccharide.
PURPOSE: The work aimed to compare quality of a siRNA carrier prepared with chitosan of two different sources having similar degree of deacetylation and molecular weights. Differences were analyzed from thermodynamic characteristics of interactions with siRNA. METHODS: The siRNA carrier (chitosan-coated poly(isobutylcyanoacrylate) nanoparticles) was prepared with home-prepared, CSLab, and commercial, CSCom, chitosans. Chitosan counterion was identified and chitosans CSCommod1 and CSCommod2 were obtained from CSCom exchanging counterion with that found on CSLab. Carrier quality was checked considering the size, zeta potential and siRNA association capacity by gel electrophoresis. Thermodynamic parameters of interactions between siRNA and chitosans in solution or immobilized at the carrier surface were determined by isothermal titration calorimetry (ITC). RESULTS: CSLab and CSCommod2 having a high content of acetate counterion associated better siRNA than CSCom and CSCommod1 which counterion included mainly chloride. ITC measurements indicated that siRNA interactions with chitosan and the siRNA carrier were driven by entropic phenomena including dehydration, but thermodynamic parameters of interactions clearly differed according to the nature of the counterion of chitosan. The influence of chitosan counterions was interpreted considering their different lyotropic character. CONCLUSION: Association of siRNA with our siRNA carrier was influenced by the nature of counterions associated with chitosan. Driven by entropic phenomena including dehydration, interactions were favored by acetate counterion. Although more work would be needed to decipher the influence of the counterion of chitosan during association with siRNA, it was pointed out as a new critical attribute of chitosan to consider while formulating siRNA carrier with this polysaccharide.
Authors: Henri de Martimprey; Jean-Rémi Bertrand; Claude Malvy; Patrick Couvreur; Christine Vauthier Journal: Pharm Res Date: 2010-01-20 Impact factor: 4.200
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Authors: Philippe Merle; Philippe Camus; Armand Abergel; Georges Philippe Pageaux; Claude Masliah; Jean Pierre Bronowicki; Jean Pierre Zarski; Gilles Pelletier; Mohamed Bouattour; Laetitia Farloux; Etienne Dorval; Gilles Verset; Si-Nafa Si-Ahmed; Michel Doffoel; Patrice Couzigou; Julien Taieb; Bérangère Vasseur; Pierre Attali Journal: ESMO Open Date: 2017-10-23