| abstract |
A cationic lipid comprising a primary group and two biodegradable hydrophobic tails, wherein (a) the primary group includes a head group and a central moiety to which both the biodegradable hydrophobic tails and the head group are directly attached, the primary group having a protonatable group with a pKa of from about 4 to about 11, (b) the cationic lipid has an in vivo half-life (t 1/2 ) in the liver of less than about 3 hours, (c) the cationic lipid has a logP value of at least 10.1, and (d) each biodegradable hydrophobic tail has the formula -(hydrophobic chain)-(biodegradable group)-(hydrophobic chain). wherein in at least one biodegradable hydrophobic tail, (i) the terminal hydrophobic chain in the hydrophobic tail is a branched alkyl group, the branching occurring at the α-position relative to the biodegradable group; (ii) the biodegradable group is separated from an end of the hydrophobic tail by 6 to 12 carbon atoms; (iii) the at least one biodegradable hydrophobic tail has the formula -R 12 -M 1 -R 13 where R 12 is a C 4 -C 14 alkylene or C 4 -C 14 alkenylene, M 1 is the biodegradable group is and R 13 is a branched C 10 -C 20 alkyl; and (iv) the total carbon atom content of the -R 12 -M 1 -R 13 tail is from 21 to 26. |