title: Comprehensive comparison of two new biodegradable gene carriers.
abstract: Safety and high transfection efficiency are the prerequisites for an ideal gene vector. Polyethylenimine (PEI), especially PEI 25k (25 kDa), is a well-known cationic gene carrier with high transfection efficiency. However, the high toxicity, depended on its molecular weight, has limited its use as a potential gene carrier. In our research, for the purpose of reducing the toxicity and increasing the transfection efficiency and further to inspect where the degradation of these biodegradable polymers take place would be more beneficial, in cytoplasm or in endocytic vesicles, two kinds of degradable polymers were synthesized. One is an acid-liable PEI derivate (PEI-GA) which was cross-linked by PEI 2k with glutadialdehyde (GA) through imine linkages and the other one (PEI-TEG) was cross-linked PEI 2k with modified triethyleneglycol (TEG) through biscarbamate linkages and can be degraded at neutral environment. By the use of a series of assay methods both in vitro and in vivo, the results showed that PEI-TEG was found to be biodegradable at neutral environment and exhibit high transfection ability with low toxicity, which indicated its potential as a candidate carrier for gene therapy.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Southern Renmin Road, Chengdu, Sichuan 610041, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Di
authors.initials: D
authors.lastname: Zhu
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D020341:Absorbable Implants; D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D003432:Cross-Linking Reagents / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000032:analysis; D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D005260:Female; D005822:Genetic Vectors / Q000032:analysis / Q000737:chemistry*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007097:Imines / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011095:Polyethylenes / Q000737:chemistry; D011108:Polymers / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014162:Transfection
chemical_list: D000447:Aldehydes; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005079:Excipients; D007097:Imines; D011095:Polyethylenes; D011108:Polymers; D013778:Tetrazolium Salts; D013844:Thiazoles; C505405:poly(ethylene imine); C028914:triethylene glycol; D011092:Polyethylene Glycols; D003850:Deoxyribonuclease I; C022616:thiazolyl blue