Succinated chitosan as a gene carrier for improved chitosan solubility and gene transfection.
Chitosan (CHI), a linear polysaccharide, has been intensively studied as a nonviral gene delivery vector. The low physiological solubility of CHI has limited its gene transfection efficiency. Here we report the synthesis of different substitution degrees of succinated chitosans (CHI-succ) to increase water solubility. According to the proton nuclear magnetic resonance spectra, the degree of deacetylation of hydrolyzed CHI was roughly 88% and the degrees of succinylation in three CHI-succ polymers were approximately 5, 10, and 20%. Various weight ratios of CHI/DNA and CHI-succ/DNA polyplexes were prepared for gel electrophoresis retardation, particle size, zeta potential, and morphology studies. The results suggest that the plasmid DNA is readily entrapped at a CHI-succ/DNA weight ratio of 20; the sizes and zeta potentials were between 110 and 140 nm and ±1-5 mV, and the polyplexes exhibited low cytotoxicity against HEK 293T cells. CHI-succ with 5 and 10% degrees of substitution showed improved transfection efficiency as compared with nascent CHI.


BACKGROUND
Chitosan, a cationic polysacchride with gene therapy potential, has inherently poor water solubility, which is improved by partial succinylation according to this report. The new DNA/Chitosan polyplexes exhibit improved safety against HEK 293T cells.
Toh
Elsie Khai-Woon
EK
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chen
Hsing-Yin
HY
Lo
Yu-Lun
YL
Huang
Shih-Jer
SJ
Wang
Li-Fang
LF
D002460:Cell Line; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism*; D004270:DNA, Circular / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D005796:Genes / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013386:Succinates / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection / Q000379:methods*; D014867:Water / Q000737:chemistry
D004270:DNA, Circular; D013386:Succinates; D014867:Water; D048271:Chitosan