Preparation of monomethyl poly (ethylene glycol)-g-chitosan copolymers with various degrees of substitution: Their ability to encapsulate and condense plasmid DNA

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作者
Zhang, Wei [1 ]
Pan, Shirong [1 ]
Zhang, Xuan [1 ]
Luo, Xin [1 ]
Du, Zhuo [1 ]
机构
[1] Cardiovascular Research Lab., First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
来源
Journal of Applied Polymer Science | 2008年 / 108卷 / 05期
关键词
Chitosan (CS) has great potential as a nonvirus gene delivery vector; but its application is limited because of poor water solubility. Monomethyl poly(ethylene glycol) (mPEG)-graft-CS copolymers were synthesized by the reaction of mPEG-aldehyde (oxidized mPEG) with amino groups on CS chains; they showed enhanced solubility in water. Copolymers with various mPEG degrees of substitution (DS) and CS molecular weights were obtained; and their capabilities of DNA encapsulation were compared through gel retardation assay and particle size and ζ potential measurements. The effects of different ratios of primary amines on CS to the phosphate groups on DNA (N/P ratios); DS; and molecular weights on particle size and encapsulation efficiency were investigated. The results show that high N/P ratios and proper DS were necessary for the formation of well-distributed complex particles. Among all of these samples; mPEG (3.55)-CS (50 kDa)/DNA complexes [where the parentheses following mPEG indicate DS (%); and the parentheses following CS indicate the molecular weight of CS] raised the ζ potential from negative to positive most quickly; yielded the smallest particle size; and were retarded in agarose gel at the lowest N/P ratio; this indicated the best efficiency of DNA encapsulation. On the contrary; mPEG (0.80)-CS (50 kDa)/DNA complexes raised the ζ potential to positive most slowly; fluctuated around the value 0 from N/P ratios of 15 : 1 to 30 : 1; and were retarded in agarose gel at the highest N/P ratio; this indicated the lowest efficiency of encapsulating plasmids. Copolymers with desirable efficiencies of DNA encapsulation could be promising gene carriers. © 2008 Wiley Periodicals; Inc;
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页码:2958 / 2967
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