Interleukin-12 Plasmid DNA Delivery by N-[(2-Hydroxy-3-trimethylammonium)propyl]chitosan-Based Nanoparticles

Polymers

Bahman Khalvati¹  Farshad Safari¹  Zahra Taheri²  Ali Dehshahri²  Abolfazl Heydari³  Reza Mohammadinejad⁴ 

[1] Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj P.O. Box 7591994779, Iran;Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz P.O. Box 7146864685, Iran;Polymer Institute of the Slovak Academy of Sciences, Dúbravská cesta 9, 845 41 Bratislava, Slovakia;Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman P.O. Box 76187-47653, Iran;

关键词: quaternized chitosan;    polyplex;    nanoparticles;    interleukin-12;    gene delivery;   

DOI  :  10.3390/polym14112176

来源: DOAJ

【 摘 要 】

Cationic polysaccharides are capable of forming polyplexes with nucleic acids and are considered promising polymeric gene carriers. The objective of this study was to evaluate the transfection efficiency and cytotoxicity of N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan salt (HTCS), a quaternary ammonium derivative of chitosan (CS), which benefits from non-ionizable positive charges. In this work, HTCS with a full quaternization of amino groups and a molar mass of 130,000 g·mol⁻¹ was synthesized to use for delivery of a plasmid encoding the interleukin-12 (IL-12) gene. Thus, a polyplex based on HTCS and the IL-12 plasmid was prepared and then was characterized in terms of particle size, zeta potential, plasmid condensation ability, and protection of the plasmid against enzymatic degradation. We showed that HTCS was able to condense the IL-12 plasmid by the formation of polyplexes in the range of 74.5 ± 0.75 nm. The level of hIL-12 production following the transfection of the cells with HTCS polyplexes at a C/P ratio of 8:1 was around 4.8- and 2.2-fold higher than with CS and polyethylenimine polyplexes, respectively. These findings highlight the role of HTCS in the formation of polyplexes for the efficient delivery of plasmid DNA.

【 授权许可】

Unknown