| Project/Area Number |
60571023
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
YOTSUYANAGI Toshihisa Faculty of Pharmaceutical Sciences, Nagoya City University, 薬学部, 助教授 (40080189)
四ッ柳 智久 (1986) 名古屋市立大学, 薬学部, 助教授
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Naoko Faculty of Pharmaceutical Sciences, Nagoya City University, 薬学部, 助手 (50117818)
IKEDA Ken Faculty of Pharmaceutical Sciences, Nagoya City University, 薬学部, 教授 (50080164)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1986: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1985: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Liposome / Freezing-thawing / Cholesterol / Sonication / Sodium cholate / Stability / Disintegration |
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| Research Abstract |
To establish liposomes as an effective drug carrier system, the relationship between the stability of the dispersed system and physical and chemical stresses will be most important. When the system is stored as a frozen state, the effect of freezing and thawing on the dispersed system should be examined, to which the properties of the system before freezing are also significantly related.
The aggregation of pure egg lecithin liposomes was induced by NaCl. The threshold concentration of NaCl was 0.15%. This result is important when even neutral liposomes is used as drug carriers, especially in the reconstitution of lyophilized liposomal systems.
The effects of sonication(physical stress) and sodium cholate(chemical stress) on the turbidity change of egg lecithin liposomes was represented by first-order disintegration rate constant(ku and ks). A plot of ku against membrane cholesterol content(CH) gave a sigmoidal curve. The plot of ks against CH gave a biphasic curve with only one inflection point. The mechanisms of disintegration of CH-rich domains and interfacial boundary lecithin are entirely different between the two stresses.
The turbidity change of egg lecithin liposomes sonicated for various periods were measured before and after freezing. Quick freezing by nitrogen gave considerable increase of the turbidity regardless of the initial size distribution. In contrast, slow freezing yielded much smaller increase with almost parallel to the initial turbidity. The slow leakage of calcein in the slow freezing may reflect minor damage of the membrane. The effect of CH on the turbidity showed a maximum at 20 mol% CH in both the slow and quick freezings. This result suggests that water content in the membrane with this molar ratio is relatively high and the membrane is readily damaged by frozen ice. Further studies using various drugs, hydrophilic and hydrophobic, are required.
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