Poly-l-glutamic acid derivatives as multifunctional vectors for gene delivery. Part B. Biological evaluation.
Cationic polymers, such as poly-l-lysine (pLL) and polyethyleneimine (pEI), are receiving growing attention as vectors for gene therapy. They form polyelectrolyte complexes with DNA, resulting in a reduced size of the DNA and an enhanced stability toward nucleases. The major disadvantages of using both polymers for in vivo purposes are their cytotoxicity and, in the case of pEI, the fact that it's not biodegradable. In this work, we investigated the interaction between a series of cationic, glutamic acid based polymers and red blood cells. The MTT test was used to investigate the cytotoxicity of the complexes. The ability of the polymers to stabilize DNA toward nucleases was investigated. Transfection studies were carried out on Cos-1 cells. The results from the haemolysis studies, the haemagglutination studies, and the MTT assay show that the polymers are substantially less toxic than pLL and pEI. The polymers are able to protect the DNA from digestion by DNase I. The transfection studies show that the polymer-DNA complexes are capable of transfecting cells, most of them with poor efficiency compared to pEI-DNA complexes.
Dubruel
Peter
P
Department of Organic Chemistry, Ghent University, Ghent, Belgium.
Dekie
Luc
L
Christiaens
Bart
B
Vanloo
Berlinda
B
Rosseneu
Maryvonne
M
Van De Kerckhove
Joel
J
Mannisto
Marjo
M
Urtti
Arto
A
Schacht
Etienne
E
D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000592:standards; D019556:COS Cells; D002417:Cattle; D004247:DNA; D004337:Drug Carriers / Q000138:chemical synthesis / Q000494:pharmacology* / Q000592:standards; D004355:Drug Stability; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006384:Hemagglutination / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D008422:Materials Testing; D011099:Polyglutamic Acid / Q000138:chemical synthesis / Q000494:pharmacology*; D014162:Transfection / Q000379:methods / Q000592:standards
D001672:Biocompatible Materials; D004337:Drug Carriers; D011099:Polyglutamic Acid; D004247:DNA