Novel macrocyclic and acyclic cationic lipids for gene transfer: synthesis and in vitro evaluation.
The synthesis and in vitro evaluation of four cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic, and saturated or unsaturated hydrophobic regions, is described. The synthesis employed standard protocols, including ring-closing metathesis for macrocyclic lipid construction. All lipoplexes studied, formulated from plasmid DNA and a liposome composed of a synthesized lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol as co-lipid, exhibited plasmid DNA binding and protection from DNase I degradation, and concentration dependent cytotoxicity using Chinese hamster ovary-K1 cells. The transfection efficiency of formulations with cholesterol outperformed those with DOPE, and in many cases the EPC/cholesterol control, and formulations with a macrocyclic lipid (+/- 10:1) outperformed their acyclic counterparts (+/- 3:1).
School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, Northern Ireland, BT9 5AG, United Kingdom. w.goldring@qub.ac.uk
William P D
WP
Goldring
Emile
E
Jubeli
Rachael A
RA
Downs
Adam J S
AJ
Johnston
Nada
N
Abdul Khalique
Liji
L
Raju
Deena
D
Wafadari
Michael D
MD
Pungente
D000818:Animals; D016466:CHO Cells; D002412:Cations / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D008055:Lipids / Q000138:chemical synthesis* / Q000494:pharmacology; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014162:Transfection
D002412:Cations; D008055:Lipids; D047028:Macrocyclic Compounds