In vitro cytotoxicity of poly(amidoamine)s: relevance to DNA delivery.
We have examined the cytotoxicity of a number of poly(amidoamine) polymers which have been proposed for use as DNA delivery systems and compared them to the charged polyamino acid polylysine. Most of the poly(amidoamine)s tested were shown to be remarkably non-toxic to both HepG2 and HL60 cell lines. However, one of the structures (NG30, co-monomers methylene bisacrylamide, dimethylethylene diamine) did show cytotoxicity similar to that of polylysine. A second PAA structure (NG37, NG38, NG39, co-monomers bisacryloyl piperazine, 2-methyl piperazine) showed mild cytotoxicity towards both cell lines, related to the degree of polymerisation. The results support the idea that the cytotoxicity of polycations has a strong structural basis rather than being an effect due only to charge. As a consequence of their general reduced level of cytotoxicity, poly(amidoamine)s appear to have possible advantages for complexation with DNA over some other cationic polymers as a key component of DNA delivery systems.
Hill
I R
IR
School of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Garnett
M C
MC
Bignotti
F
F
Davis
S S
SS
D002411:Cation Exchange Resins; D004247:DNA / Q000737:chemistry*; D004337:Drug Carriers; D018014:Gene Transfer Techniques; D018922:HL-60 Cells; D006801:Humans; D008055:Lipids; D008156:Luciferases; D010957:Plasmids; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011107:Polylysine / Q000633:toxicity; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods
D002411:Cation Exchange Resins; D004337:Drug Carriers; D008055:Lipids; C086724:Lipofectamine; D011073:Polyamines; D011108:Polymers; D011107:Polylysine; D004247:DNA; D008156:Luciferases