Polymerization of Diene-Containing Lipids as Liposomes by Radical Initiators. 4. Effect of Lipid Packing on the Polymerization Profile

l,2-Di(2,4-octadecadienoyl)-sn-glycero-3-phosphorylcholine (DODPC) was polymerized as liposomes with a water-soluble radical initiator, azobis(2-amidinopropane) dihydrochloride (AAPD). DODPC liposomes were prepared with a tip-type sonicator and incubated at 4, 8, or 20 °C. When DODPC liposomes were incubated at lower temperatures than the gel-to-liquid crystalline phase transition temperature (16 deC for DODPC liposomes), these liposomes fused with each other to produce large unilamellar liposomes. An average radius was calculated from the ¹H NMR signal intensity ratio for the choline methyl protons split by Eu³⁺. Generally AAPD initiated radical polymerization of diene groups on the 2-acyl chains of DODPC because of nonequivalent acyl chain packing in bilayer membranes. The polymerization conversion for larger DODPC liposomes reached about 50% by AAPD-initiated polymerization. An excess polymerization was initiated by AAPD when liposomes were not incubated unless the average radius was smaller than 30 nm. This is explained by the disordered lipid packing for small liposomes. This disordered lipid packing permits invasion of water molecules deeper into the hydrophobic region of the outer half of the bilayer membrane of the liposomes, attributed to a larger curvature. For small DODPC liposomes the AAPD radicals could therefore reach diene groups in even 1-acyl chains which were essentially not attacked by AAPD radicals from an aqueous phase as long as lipids were well oriented. The increase of polymerization conversion may be due to an entropically semistable lipid packing inevitable for smaller liposomes. It is concluded that the well-defined selective polymerization of diene groups in 2-acyl chains of DODPC lipids requires liposomes larger in size than with a 30-nm radius.