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Counterion of Chitosan Influences Thermodynamics of Association of siRNA with a Chitosan-Based siRNA Carrier

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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.

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Abbreviations

CS:

Generic abbreviation for chitosans used in this work

CSLab :

Chitosan prepared in our lab

CSCom :

Commercial chitosan

CSCom-mod1:

Commercial chitosan modified with method 1

CSCom-mod2:

Commercial chitosan modified with method 2

DeltaH :

Normalized enthalpy

ΔH fit :

Interaction enthalpy deduced from the fit of the curve and using Eq. 5

ΔH graph :

Interaction enthalpy evaluated from graphs

ΔG :

Difference in free energy

ΔS :

Entropy of the reaction

D H :

Hydrodynamic diameter

ITC:

Isothermal titration calorimetry

K a :

Association constant

K d :

Dissociation constant

NP CSxxx :

Nanoparticles prepared with the specified chitosan

NP CSxxx-P:

Nanoparticles prepared with the specified chitosan and poloxamer 188

NP P:

Nanoparticles prepared with poloxamer 188

PACA:

Poly(alkylcyanoacrylate)

siRNA:

Small interfering RNA

-TΔS :

Entropic therms of the reaction

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ACKNOWLEDGMENTS AND DISCLOSURES

Financial support was obtained from INNABIOSANTE, Toulouse, France project NANOINTERFERENCE.

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  1. Institut Galien Paris-Sud, CNRS UMR 8612, Univ Paris-Sud, Faculté de Pharmacie, 5 rue J.B. Clément, 92296, Châtenay-Malabry Cedex, France

    Christelle Zandanel, Magali Noiray & Christine Vauthier

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  1. Christelle Zandanel
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Zandanel, C., Noiray, M. & Vauthier, C. Counterion of Chitosan Influences Thermodynamics of Association of siRNA with a Chitosan-Based siRNA Carrier. Pharm Res 37, 22 (2020). https://doi.org/10.1007/s11095-019-2751-z

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