Synthesis and characterization of betaine-like diacyl lipids: zwitterionic lipids with the cationic amine at the bilayer interface.
We synthesized and characterized a series of zwitterionic, acetate-terminated, quaternized amine diacyl lipids (AQ). These lipids have an inverted headgroup orientation as compared to naturally occurring phosphatidylcholine (PC) lipids; the cationic group is anchored at the membrane interface, while the anionic group extends into the aqueous phase. AQ lipids preferentially interact with highly polarizable anions (ClO(4)(-)) over less polarizable ions (Cl(-)), in accord with the Hofmeister series, as measured by the change in zeta potential of AQ liposomes. Conversely, AQ lipids have a weaker association with calcium than do PC lipids. The transition temperatures (Tm) of the AQ lipids are similar to the Tm observed with phosphatidylethanolamine (PE) lipids of the same chain length. AQ lipids form large lipid sheets after heating and sonication; however, in the presence of cholesterol (Chol), these lipids form stable liposomes that encapsulate carboxyfluorescein. The AQ:Chol liposomes retain their contents in the presence of serum at 37°C, and when injected intravenously into mice, their organ biodistribution is similar to that observed with PC:Chol liposomes. AQ lipids demonstrate that modulating the headgroup charge orientation significantly alters the biophysical properties of liposomes. For the drug carrier field, these new materials provide a non-phosphate containing zwitterlipid for the production of lipid vesicles.
The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California Berkeley, Berkeley, CA 94720-1762, United States.
Aditya G
AG
Kohli
Colin L
CL
Walsh
Francis C
FC
Szoka
D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry*; D001622:Betaine / Q000031:analogs & derivatives*; D008051:Lipid Bilayers / Q000138:chemical synthesis / Q000737:chemistry*; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties; D044366:Transition Temperature
D000085:Acetates; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D001622:Betaine