Facile synthesis of phosphatidyl saccharides for preparation of anionic nanoliposomes with enhanced stability.
Physical stability during storage and against processing such as dehyration/rehydration are the cornerstone in designing delivery vehicles. In this work, mono-, di- and tri-saccharides were enzymatically conjugated to phosphatidyl group through a facile approach namely phospholipase D (PLD) mediated transphosphatidylation in a biphasic reaction system. The purified products were structurally identified and the connectivities of carbohydrate to phosphatidyl moiety precisely mapped by (1)H, (31)P, (13)C NMR pulse sequences and LC-ESI-FTMS. The synthetic phosphatidyl saccharides were employed as the sole biomimetic component for preparation of nanoliposomes. It was found that the critical micelle concentration (CMC) of phosphatidyl saccharides increases as more bulky sugar moiety (mono- to tri-) is introduced. Phosphatidyl di-saccharide had the largest membrane curvature. In comparison to the zwitterionic phosphatidylcholine liposome, all phosphatidyl saccharides liposomes are anionic and demonstrated significantly enhanced stability during storage. According to the confocal laser scan microscopy (CLSM) and atom force microscopy (AFM) analyses, the nanoliposomes formed by the synthetic phosphatidyl saccharides also show excellent stability against dehydration/rehydration process in which most of the liposomal structures remained intact. The abundance hydroxyl groups in the saccharide moieties might provide sufficient H-bondings for stabilization. This work demonstrated the synthesized phosphatidyl saccharides are capable of functioning as enzymatically liable materials which can form stable nanoliposomes without addition of stabilizing excipients.
Department of Engineering, Aarhus University, Aarhus, Denmark ; College of Life Science and Technology, Beijing University of Chemical Technology (BUCT), Beijing, China.
Shuang
S
Song
Ling-Zhi
LZ
Cheong
Mia
M
Falkeborg
Lei
L
Liu
Mingdong
M
Dong
Henrik Max
HM
Jensen
Kresten
K
Bertelsen
Michael
M
Thorsen
Tianwei
T
Tan
Xuebing
X
Xu
Zheng
Z
Guo
D000838:Anions / Q000737:chemistry*; D002241:Carbohydrates / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D015394:Molecular Structure; D036103:Nanotechnology; D055601:Organic Chemistry Phenomena
D000838:Anions; D002241:Carbohydrates; D008081:Liposomes