NDLI: N $^{1}$,N $^{ 12 }$-Diacyl Spermines: SAR Studies on Non-viral Lipopolyamine Vectors for Plasmid DNA and siRNA Formulation

Content Provider	Springer Nature Link
Author	Ghonaim, Hassan M. Li, Shi Blagbrough, Ian S.
Copyright Year	2008
Abstract	To study the efficiency of novel synthetic N $^{1}$,N $^{12}$-diacyl spermines on DNA and siRNA binding, and to compare their transfection efficiency with viability in cell lines.Five long chain N $^{1}$,N $^{12}$-diacyl lipopolyamines: N $^{1}$,N $^{12}$-[didecanoyl, dimyristoyl, dimyristoleoyl, distearoyl and dioleoyl]-1,12-diamino-4,9-diazadodecane were synthesized from the naturally occurring polyamine spermine. Their abilities to condense DNA and to form nanoparticles were characterized. Transfection efficiencies were studied in FEK4 primary skin cells and in an immortalized cancer cell line (HtTA), and compared with N $^{4}$,N $^{9}$-regioisomers. Also, the abilities of these novel compounds to bind to siRNA-forming nanoparticles were studied using a RiboGreen intercalation assay, and their abilities to deliver fluorescein-tagged siRNA into cells were quantified and compared with TransIT-TKO.By incorporating two long aliphatic chains and varying their acylation position, length, and oxidation state in a stepwise manner, we show efficient p and siRNA formulation and delivery to primary skin and cancer cell lines. Although two C14 chains (both saturated or both mono-cis-unsaturated) were efficient transfecting agents, they were highly toxic. N $^{1}$,N $^{12}$-Dioleoyl spermine efficiently binds to and delivers pDNA and siRNA with high cell viability even in a primary skin cell line. It is a novel, efficient non-viral vector in the presence of serum.
Starting Page	17
Ending Page	29
Page Count	13
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	27
Issue Number	1
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2009-10-30
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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