Liposomes are lipid bilayer vesicles. Because it is believed that natural biomembranes have a lipid bilayer structure, liposomes have been used widely as models of biomembranes as in studies on the physicochemical properties thereof. Further, liposomes have been employed as carriers for transporting substances into living organisms, because various substances can be enclosed within the internal aqueous phase or within the membrane of the liposomes and liposomes can fuse with cells or become incorporated into cells.
Thus, liposomes have been used extensively in research, for example, in biology, medicine and pharmacology. Attempts have been made to use liposomes as a carrier for transporting enzymes or carcinostatic substances, for immunological purposes, for achieving mutual interactions with cells or as a drug delivery system.
Although liposomes are widely applicable as described above, liposomes often are disadvantageous because of a rigid membrane structure.
That is to say, it is observed frequently that the orientation of the membrane of a liposome is disordered by a chemical or physical change in the lipids constituting the membrane. As a result, liposomes suffer from leakage of contents or the association or aggregation with other liposomes, resulting in precipitation.
To overcome the disadvantages, attempts have been made to form vesicles using synthetic amphipathic compounds imitating natural phospholipids (refer to, for example, "Liposome", Nojima, Sunamoto and Inoue, (Nankodo), chap. 8). However none of the amphipathic compounds is satisfactory as a drug carrier with a stable vesicle or which is non-toxic.
Known examples of amphipathic compounds having an oligopeptide in the hydrophilic moiety and two long-chain alkyl groups in the hydrophobic moiety include those reported by Ihara et al. (Polym. Commun., 27, 282 (1986); Polymer J., 18, 163 (1986); Chem. Lett., 1713 (1984); and J. Jap. Chem., 543 (1987); and those reported by Shimizu et al. (Chem. Lett., 1341 (1989); Thin Solid Films., 180, 179 (1989); JP-A-2-69498; and JP-A-2-71836) (The term "JP-A" as used herein means an "unexamined published Japanese patent application"). However none of these amphipathic compounds is suitable as a drug carrier because they do not form a unilayer vesicle or the unilayer vesicle, if formed, is converted readily into other structures. Further, every molecule aggregate comprising the compounds is charged positively and thus cannot be used as an appropriate model of a biomembrane containing anionic lipids such as phosphatidylserine or phosphatidylglycerol.
USPTO Backgrounds
USPTO Backgrounds