Control of release of encapsulated molecules from polymerized mixed liposomes induced by physical or chemical stimuli

Takeoka Shinji, Ohno Hiroyuki, Hayashi Narutoshi, Tsuchida Eishun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Small unilamellar mixed liposomes composed of polymerizable and non-polymerizable lipids are polymerized to prepare stimuli-responsive polymerized liposomes. Encapsulated 5(6)-carboxyfluorescein (CF) is released from non-polymerizable regions by physical and/or chemical stimuli. As the liposome structure is maintained by polymerized lipid frames, the release is stopped by removing the stimuli. This process can be repeated several times. CF is released rapidly at the phase transition temperature of the non-polymerizable lipids, e.g., at 37 and 19°C for dipalmitoylphosphatidylcholine and dimyristoylphosphatidykholine, respectively. The temperature dependence is further affected by the size of the phase-separated domains. Polymerized mixed liposomes having larger phase-separated domains show a sharper response to the phase transition. In case of polymerized mixed liposomes containing phosphatidylethanolamine, CF is released as a function of pH. The release rate is very small at pH 11, but it increases with pH decreasing to 7.5, which is attributed to the structural change of the bilayer induced by the change in dissociation of the head groups. On the other hand, in case of polymerized mixed liposomes containing phosphatidylserine, release of CF is accelerated by the addition of Ca2+ ions and is restored to the initial rate by eliminating Ca2+ ions with ethylenediamine tetraacetic acid sodium salt (EDTA). The CF release response is obtained repeatedly by the alternating addition of Ca2+ ion and EDTA.

Original languageEnglish
Pages (from-to)177-186
Number of pages10
JournalJournal of Controlled Release
Issue number2
Publication statusPublished - 1989 Jul

ASJC Scopus subject areas

  • Pharmaceutical Science


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