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A novel, non-toxic chitosan modified with lysine to enhance buffer capacity for siRNA delivery
Author(s)
Tianhui Liu Department of Pharmacy, School of Pharmacy and Medical Technology, Putian University, Putian, China; Key Laboratory of Pharmaceutical Analysis and Laboratory Medicine in University of Fujian Province, Putian University, Putian, China
Mei Lin Department of Medicinal Chemistry, School of Pharmacy, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fuzhou, China
Chengfei Zhao Department of Pharmacy, School of Pharmacy and Medical Technology, Putian University, Putian, China; Key Laboratory of Pharmaceutical Analysis and Laboratory Medicine in University of Fujian Province, Putian University, Putian, China
Aizhu Lin Key Laboratory of Technical Evaluation of Fertility Regulation of Non-Human Primates, National Health Commission, Fuzhou, China; Fujian Obstetrics and Gynecology Hospital, Fuzhou, China
Abstract
The present study employed lysine as a modifying agent for chitosan (CS) to synthesise a novel CS derivative (LGCS) intended for siRNA delivery. The successful grafting of lysine to CS was characterized using FT-IR and the introduction of the lysine moiety resulted in improved solubility and buffering capacity of CS. The Zeta potential and size of LGCS/siRNA nanoparticles (NPs) were evaluated using dynamic light scattering (DLS) and the results were verified by transmission electron microscopy (TEM). Evaluation of LGCS's siRNA binding capacity was conducted using a gel retardation assay. The results showed that LGCS could effectively bind to siRNA and form a complex with a hydrated diameter of about 97.2 ± 1.3 nm. Furthermore, cytotoxicity assays conducted on RSC96 cells demonstrated that LGCS exhibited lower toxicity compared to linear polyethyleneimine (PEI) 25k. In vitro, cellular uptake assays also revealed that LGCS displayed excellent transfection efficiency. The results of our study lead us to the conclusion that LGCS holds great promise as a gene delivery vector.
Publication Details
Page(s) 903-915
DOI 10.36721/PJPS.2024.37.4.REG.903-915.1
Published Journal: Pakistan Journal of Pharmaceutical Sciences, Volume: 37, Issue: 4, Year: 2024
Keywords
Chitosan Lysine selfassembly nonviral vectors Cationic polymerization
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