Formation of homogeneous unilamellar liposomes from an interdigitated matrix |
| |
Authors: | Alla Polozova Xingong Li Tong Shangguan Daniel R. Schuette Sol M. Gruner |
| |
Affiliation: | a Elan Drug Delivery, 1 Research Way, Princeton, NJ 08540, United States b Physics Department, Cornell University, Ithaca, NY 14853, United States |
| |
Abstract: | Phospholipid-ethanol-aqueous mixtures containing bilayer-forming lipids and 20-50 wt.% of water form viscous gels. Further hydration of these gels results in the formation of liposomes whose morphology depends upon the lipid type. Upon hydration of gels containing mixtures of the lipids 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG), small homogeneous and unilamellar liposomes were produced. In contrast, hydration of gels containing only POPC resulted in formation of large multilamellar liposomes. Likewise, mulitlamellar liposomes resulted when this method was applied to form highly fusogenic liposomes comprised of the novel negatively charged N-acyl-phosphatidylethanolamine (NAPE) mixed with di-oleoyl-phosphatidylcholine (DOPC) (7:3) [T. Shangguan, C.C. Pak, S. Ali, A.S. Janoff, P. Meers, Cation-dependent fusogenicity of an N-acyl phosphatidylethanolamine, Biochim. Biophys. Acta 1368 (1998) 171-183]. In all cases, the measured aqueous entrapment efficiencies were relatively high. To better understand how the molecular organization of these various gels affects liposome morphology, we examined samples by freeze-fracture transmission electron microscopy and X-ray diffraction. We found that phospholipid-ethanol-water gels are comprised of highly organized stacks of lamellae. A distinct feature of the gel samples that result in small unilamellar liposomes is the combination of acyl chain interdigitation and net electrostatic charge. We speculate that the mechanism of unilamellar liposome formation proceeds via formation of stalk contacts between neighboring layers similar to membrane hemifusion intermediates, and the high aqueous entrapment efficiencies make this liposome formation process attractive for use in drug delivery applications. |
| |
Keywords: | POPC, palmitoyl-oleoyl-phosphatidylcholine POPG, palmitoyl-oleoyl-phosphatidylglycerol DOPC, di-oleoyl-phosphatidylcholine NBD-PE, nitrobenzoxadiazol-phoshatydylethanolamine NAPE, N-acyl-phosphatidylethanolamine DPPC, di-palmitoyl-phoshatidylcholine DSPC, di-stearoyl-phosphatidylcholine SUV, small unilamellar vesicles |
本文献已被 ScienceDirect 等数据库收录! |
|