Temperature-sensitive releases from liposomes containing hydrophobically modified poly(N-isopropylacrylamide)

Novel temperature-sensitive liposomes containing hydrophobically modified poly(N-isopropylacrylamide) (HPNIPAM) and their release behaviors were investigated using calcein as a fluorescence probe. Above the lower critical solution temperature (LCST) of the polymer (e.g., 40 degrees C), the degree of calcein release in 280 sec from reverse-phase evaporation vesicles (REVs) of egg phosphatidylcholine (egg PC) was 43 %, while egg PC MLVs was 16 %. Such a large difference of release may be attributed to the lamellarity of liposomes. The incorporation of dioleoylphosphatidylethanolamine (DOPE) into the PC bilayer enhanced the release by 10-13 % at 40 degrees C, probably due to the increased instability of mixture bilayers. Meanwhile, a temperature-sensitive device of DOPE liposomes was prepared by using HPNIPAM as a stabilizer. The optimal ratio of HPNIPAM to lipid to stabilize the bilayer was 0.1. Above the LCST (e.g., 40 degrees C), the release percentage was about 80 % of the entrapped calcein. DOPE liposomes were the most temperature-sensitive among liposomes tested. This is probably because DOPE liposomes disintegrate into a non-liposomal phase, such as hexagonal (H-Pi), by a thermal contraction of HPNIPAM.