TY - JOUR
T1 - Spontaneous liposome formation induced by grafted poly(ethylene oxide) layers
T2 - Theoretical prediction and experimental verification
AU - Szleifer, Igal
AU - Gerasimov, Oleg V.
AU - Thompson, David H.
PY - 1998/2/3
Y1 - 1998/2/3
N2 - Spontaneous liposome formation is predicted in binary mixtures of fluid phase phospholipids and poly(n)ethylene oxide (PEO)-bearing lipids by using single chain mean field theory. The range of stability of the spontaneous liposomes is determined as a function of percentage of PEO-conjugated lipids and polymer molecular weight. These predictions were tested by using cast films of 1,2-diacyl-sn-glycerophosphocholines (e.g., egg L-α-lecithin, 1,2- dimyristoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3- phosphocholine, and 1,2-distearoyl-sn-glycero-3-phosphocholine) and 1,2- dipalmitoyl-sn-glycerophosphatidylethanolamine-PEO conjugates (i.e., 1,2- dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxypoly(ethylene glycol)2000]carboxamide and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine- N-[methoxypoly(ethylene oxide)5000] carboxamide) that were hydrated above their gel-liquid crystal phase transition temperatures. Particle sizes of the resulting dispersions, analyzed by quasielastic light scattering, solute retention, 31P NMR, and freeze-fracture electron microscopy measurements, confirmed the single chain mean field predictions. These data indicate that thermodynamically stable, unilamellar liposomes are formed spontaneously by simple hydration of fluid phase phospholipid bilayer films containing low molar ratios of PEO-based amphiphiles. They further suggest that the equilibrium size and colloidal properties of fluid phase, PEO-modified liposomes can be predicted by using this theoretical approach. The implication of these results on the design and processing of sterically stabilized liposomes used in drug delivery applications also is described.
AB - Spontaneous liposome formation is predicted in binary mixtures of fluid phase phospholipids and poly(n)ethylene oxide (PEO)-bearing lipids by using single chain mean field theory. The range of stability of the spontaneous liposomes is determined as a function of percentage of PEO-conjugated lipids and polymer molecular weight. These predictions were tested by using cast films of 1,2-diacyl-sn-glycerophosphocholines (e.g., egg L-α-lecithin, 1,2- dimyristoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3- phosphocholine, and 1,2-distearoyl-sn-glycero-3-phosphocholine) and 1,2- dipalmitoyl-sn-glycerophosphatidylethanolamine-PEO conjugates (i.e., 1,2- dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxypoly(ethylene glycol)2000]carboxamide and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine- N-[methoxypoly(ethylene oxide)5000] carboxamide) that were hydrated above their gel-liquid crystal phase transition temperatures. Particle sizes of the resulting dispersions, analyzed by quasielastic light scattering, solute retention, 31P NMR, and freeze-fracture electron microscopy measurements, confirmed the single chain mean field predictions. These data indicate that thermodynamically stable, unilamellar liposomes are formed spontaneously by simple hydration of fluid phase phospholipid bilayer films containing low molar ratios of PEO-based amphiphiles. They further suggest that the equilibrium size and colloidal properties of fluid phase, PEO-modified liposomes can be predicted by using this theoretical approach. The implication of these results on the design and processing of sterically stabilized liposomes used in drug delivery applications also is described.
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U2 - 10.1073/pnas.95.3.1032
DO - 10.1073/pnas.95.3.1032
M3 - Article
C2 - 9448280
AN - SCOPUS:0032477731
SN - 0027-8424
VL - 95
SP - 1032
EP - 1037
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -