Very long chain N4,N9-diacyl spermines: non-viral lipopolyamine V vectors for efficient plasmid DNA and siRNA delivery
Ghonaim, H. M., Li, S. and Blagbrough, I. S., 2009. Very long chain N4,N9-diacyl spermines: non-viral lipopolyamine V vectors for efficient plasmid DNA and siRNA delivery. Pharmaceutical Research, 26 (1), pp. 19-31.
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The five novel very long chain N (4),N (9)-diacyl polyamines: N (4),N (9)-[diarachidoyl, diarachidonoyl, dieicosenoyl, dierucoyl and dinervonoyl]-1,12-diamino-4,9-diazadodecane were synthesized. The abilities of these novel compounds to condense DNA and to form nanoparticles were studied using ethidium bromide fluorescence quenching and nanoparticle characterization techniques. Transfection efficiency was studied in FEK4 primary skin cells and in an immortalized cancer cell line (HtTA), and compared with the non-liposomal transfection formulation Lipogen, N (4),N (9)-dioleoyl-1,12-diamino-4,9-diazadodecane. Also, the abilities of these compounds to condense siRNA and to form nanoparticles were studied using a RiboGreen intercalation assay and their abilities to deliver siRNA into cells were studied in FEK4 and HtTA cells using fluorescein-labelled Label ITA (R) RNAi Delivery Control, a sequenced 21-mer from Mirus. We show efficient pEGFP and siRNA formulation and delivery to primary skin and cancer cell lines. Adding two C20 or C22 chains, both mono-cis-unsaturated, N (4),N (9)-dieicosenoyl spermine and N (4),N (9)-dierucoyl spermine, gave efficient siRNA delivery vectors, even in the presence of serum, comparable to TransIT-TKO and with excellent cell viability.
|Creators||Ghonaim, H. M., Li, S. and Blagbrough, I. S.|
|Departments||Faculty of Science > Pharmacy & Pharmacology|
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