The effects of glucose oligomers (maltodextrins) on freeze-drying liposomes.
Liposomes were freeze-dried with glucose oligomers (maltodextrins) consisting of 2 (maltose) to 7 (maltoheptaose) glucoside units, and the effects of the glucoside unit number of the maltodextrin on the lyophilization of the liposomes were investigated. When the molar ratio of the glucoside units of maltodextrins to lipids was reduced below 6, two distinct endotherms were observed after annealing the freeze-dried L-alpha-dipalmitoylphosphatidylcholine (DPPC) liposome by differential scanning calorimetry (DSC). When the molar ratio was raised above 6, only the lower of the two endotherms was observed in all maltodextrins tested. At a molar ratio of 6, the gel to liquid crystalline transition temperature (Tm) of the first scan of these samples was measured. The Tm with maltose was observed to be ca. 65 degrees C, whereas the Tm with the other maltodextrins was observed to increase as the number of glucoside units was increased. Using Fourier transform IR, the phosphate asymmetric stretching band of DPPC liposomes lyophilized with these maltodextrins was observed to shift to lower frequencies. In all cases, the phosphate asymmetric stretching was observed to be roughly 1240 and 1224 cm-1 in the presence of these saccharides. The ratio of the absorbance at 1224 to that at 1240 cm-1 of DPPC liposomes freeze-dried with maltose was greater than the ratio of those stabilized with any of the other maltodextrins tested. These results suggest that the rate of hydrogen bonding between the phosphate of the lipid and maltodextrins was highest when maltose was used as the cryoprotectant. Because of this interaction, the space between the lipid molecules may become wider, causing an increase in the flexibility of the liposomal membrane.
Ozaki
K
K
Pharmaceuticals Development Laboratory, Mitsubishi Chemical Corporation, Ibaraki, Japan.
Hayashi
M
M
D015060:1,2-Dipalmitoylphosphatidylcholine; D002240:Carbohydrate Sequence; D003451:Cryoprotective Agents / Q000737:chemistry*; D005452:Fluoresceins / Q000032:analysis; D005612:Freeze Drying; D006027:Glycosides / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008320:Maltose / Q000737:chemistry; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
D003451:Cryoprotective Agents; D005452:Fluoresceins; D006027:Glycosides; D008081:Liposomes; D011134:Polysaccharides; D015060:1,2-Dipalmitoylphosphatidylcholine; D008320:Maltose; C008315:maltodextrin; C007740:fluorexon