Amphiphilic Chitosan Bearing Double Palmitoyl Chains and Quaternary Ammonium Moieties as a Nanocarrier for Plasmid DNA

Thev Pol; Wunpen Chonkaew; Lalintip Hocharoen; Nakorn Niamnont; Namphueng Butkhot; Yaowaluck Maprang Roshorm; Suda Kiatkamjornwong; Voravee P Hoven; Kornkanya Pratumyot

doi:10.1021/acsomega.1c06101

Amphiphilic Chitosan Bearing Double Palmitoyl Chains and Quaternary Ammonium Moieties as a Nanocarrier for Plasmid DNA

ACS Omega. 2022 Mar 17;7(12):10056-10068. doi: 10.1021/acsomega.1c06101. eCollection 2022 Mar 29.

Authors

Affiliations

¹ Organic Synthesis, Electrochemistry & Natural Product Research Unit, Department of Chemistry, Faculty of Science, King Mongkut's University of Technology Thonburi, Pracha Uthit Road, Bang Mod, Thung Khru, Bangkok 10140, Thailand.
² Sustainable Polymer & Innovative Composite Materials Research Group, Department of Chemistry, Faculty of Science, King Mongkut's University of Technology Thonburi, Pracha Uthit Road, Bang Mod, Thung Khru, Bangkok 10140, Thailand.
³ Bioprocess Research and Innovation Centre (BRIC), National Biopharmaceutical Facility (NBF), King Mongkut's University of Technology Thonburi (KMUTT), Bangkhuntian-Chai Thale Road, Tha Kham, Bangkhuntian, Bangkok 10150, Thailand.
⁴ Division of Biotechnology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkhuntian-Chai Thale Road, Tha Kham, Bangkhuntian, Bangkok 10150, Thailand.
⁵ FRST, Academy of Science, Office of the Royal Society, Sanam Suea Pa, Khet Dusit, Bangkok 10300, Thailand.
⁶ Office of Research Affairs, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand.
⁷ Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand.
⁸ Center of Excellence in Materials and Bio-interfaces, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand.

Abstract

Amphiphilic chitosan, bPalm-CS-HTAP, having N-(2-((2,3-bis(palmitoyloxy)propyl)amino)-2-oxoethyl) (bPalm) groups as double hydrophobic tails and O-[(2-hydroxyl-3-trimethylammonium)] propyl (HTAP) groups as hydrophilic heads was synthesized and evaluated for its self-assembly properties and potential as a gene carrier. The degree of bis-palmitoyl group substitution (DS _bPalm) and the degree of quaternization (DQ) were approximately 2 and 56%, respectively. bPalm-CS-HTAP was found to assemble into nanosized spherical particles with a hydrodynamic diameter (D _H) of 265.5 ± 7.40 nm (PDI = 0.5) and a surface charge potential of 40.1 ± 0.04 mV. bPalm-CS-HTAP condensed the plasmid pVAX1.CoV2RBDme completely at a bPalm-CS-HTAP:pDNA ratio of 2:1. The self-assembled bPalm-CS-HTAP/pDNA complexes could enter HEK 293A and CHO cells and enabled gene expression at negligible cytotoxicity compared to commercial PEI (20 kDa). These results suggested that bPalm-CS-HTAP can be used as a promising nonviral gene carrier.