siRNA delivery with chitosan: influence of chitosan molecular weight, degree of deacetylation and amine to phosphate ratio on in vitro silencing efficiency, hemocompatibility, biodistribution and in vivo efficacy.

siRNA delivery with chitosan: influence of chitosan molecular weight, degree of deacetylation and amine to phosphate ratio on in vitro silencing efficiency, hemocompatibility, biodistribution and in vivo efficacy. Biomacromolecules. 2017 Dec 06;: Authors: Alameh MG, Lavertu M, Tran-Khanh N, Chang CY, Lesage F, Bail M, Darras V, Chevrier A, Buschmann MD Abstract Chitosan (CS) shows in vitro and in vivo efficacy for siRNA delivery, but with contradictory findings for incompletely characterized systems. To understand which parameters produce effective delivery, a library of precisely characterized chitosans was produced at different DDAs and Mn. Encapsulation and transfection efficiencies were characterized in vitro. Formulations were selected to examine the influence of Mn and N:P ratio on nanoparticle uptake, metabolic activity, genotoxicity, and in vitro transfection. Hemocompatibility and in vivo biodistribution were then investigated for different Mn, N:P ratio, and dose. Nanoparticle uptake and gene silencing correlated with increased surface charge, which was obtained at high DDA and high Mn. A minimum polymer length of ~60-70 monomers (~10kDa) was required for stability and knockdown. In vitro knockdown was equivalent to lipid control with no metabolic or genotoxicity. An inhibitory effect of serum on biological performance was dependent on DDA, Mn and N:P. In vivo biodistribution in mice show accumulation of nanoparticles in kidney, with 40-50% fun...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research

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