Cryoprotective effects of saccharides on the freeze-drying of sonicated vesicles of the novel lipid A analog, E5531.
A sonicated dispersion of the novel lipid A analog, E5531, was feeze-dried in the presence of various additives such as saccharides and polyalcohols, and their cryoprotective effects were investigated. Fusion of the vesicles was examined by measuring fluorescence energy transfer and size distribution. Cryoprotective ability differed among the addtive species. The addition of polyalcohols led to considerable fusion. Although monosaccharides, similar to disaccharides, completely prevented the fusion of the vesicles during lyophilization, they showed far less ability to retain the entrapped calcein in the vesicles compared to disaccharides. Differential scanning calorimetry heating profiles of vesicles that had been lyophilized with various additives were obtained. Disaccharides and monosaccharides again resulted in markedly different thermal properties of the vesicles. This variety in cryoprotective ability of saccharide species can be attributed to differences in their interaction with the E5531 head group.
Asai
Yasuyuki
Y
Formulation Research Laboratory Kawashima Eisai Co., Ltd. 1 Takahaya-machi, Kawashima-cho, Hashima-gun, Gifu 501-6195, Japan. y2-asai@hhc.eisai.co.jp
D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005452:Fluoresceins / Q000737:chemistry; D005612:Freeze Drying; D005947:Glucose / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D008050:Lipid A / Q000031:analogs & derivatives* / Q000737:chemistry; D010316:Particle Size; D013696:Temperature; D014465:Ultrasonics
D002241:Carbohydrates; D005079:Excipients; D005452:Fluoresceins; D008050:Lipid A; C092845:E 5531; D005947:Glucose; D007785:Lactose; C007740:fluorexon