Showing papers by "Pieter R. Cullis published in 1986"
TL;DR: Freeze-fracture electron microscopy revealed that vesicles produced at very high lipid concentrations exhibit size distributions and extent of multilamellar character comparable to systems produced at lower lipid levels.
1,689 citations
TL;DR: The straight-forward hydration of lipid to produce multilamellar vesicles (MLVs) results in systems which exhibit low trapped volumes and where solutes contained in the aqueous buffer are partially excluded from the MLV interior.
432 citations
TL;DR: It is demonstrated here that adriamycin can be rapidly and efficiently accumulated into egg phosphatidylcholine and egg PC-cholesterol LUVs in response to a transmembrane pH gradient (interior acidic) in the absence of ionophores.
368 citations
TL;DR: Evidence is reviewed supporting the proposal that factors related to the polymorphic capabilities of lipids provide a rationale for lipid diversity, which is related to a generalized shape property.
363 citations
TL;DR: The variety of procedures available for trapping hydrophilic and hydrophobic compounds are reviewed and considerations which are addressed include factors influencing the choice of a particular liposomal system and techniques for the passive entrapment of drugs in multilamellar vesicles and unilameller vesicle.
192 citations
TL;DR: The demonstration that anti-phospholipid antibodies are able to distinguish between different structural arrangements of phospholipids may have important implications regarding the immunoregulation of autoimmunity.
125 citations
Patent•
24 Jun 1986TL;DR: In this article, a multilamellar vesicle was prepared by dispersing the lipid in an aqueous phase to form a multilevelar vESicle, rapidly freezing the multilamesllar VESicle to obtain a frozen lipid-aqueous medium mixture, and warming the mixture to obtain the frozen and thawed multilAMEllar DVS.
Abstract: A multilamellar vesicle dispersed in an aqueous phase comprising an aqueous medium, a lipid concentration of at least about 50 mg/ml and a trapping efficiency of at least about 30 percent. The vesicle can be prepared by dispersing the lipid in an aqueous phase to form a multilamellar vesicle, rapidly freezing the multilamellar vesicle to obtain a frozen lipid-aqueous medium mixture, and warming the mixture to obtain a frozen and thawed multilamellar vesicle dispersed in an aqueous phase.
117 citations
Patent•
15 Dec 1986TL;DR: In this article, a composition consisting of liposomes covalently or non-covalently coupled to the glycoprotein streptavidin was described, which can be used in diagnostic assays.
Abstract: The present invention describes a composition consisting of liposomes covalently or non-covalently coupled to the glycoprotein streptavidin. The streptavidin may additionally be coupled to biotinated proteins such as Immunoglobulin G or monoclonal antibodies. The liposomes of the invention may have a transmembrane potential across their membranes, and may be dehydrated. In addition, the composition may contain ionizable bioactive agents such as antineoplastic agents, and may be used in diagnostic assays.
107 citations
60 citations
TL;DR: In this article, the correlation between phase determinations by 31P-NMR and small-angle X-ray diffraction has been investigated and it is demonstrated that the correlation is excellent, supporting the general utility of the 31P NMR method.
46 citations
TL;DR: It is concluded that complement channels are only transiently open in liposomes, and that loss of channel patency may be due to either channel closing or to loss of channels.
TL;DR: The polymorphic phase behavior of aqueous dispersions of 1-oleoyl, 1-linolenoyl-sn-3-glycerophosphoethanolamine, and 1-C18:1c-PE has been investigated by 31P NMR, small-angle and wide-angle X-ray diffraction, and freeze-fracture techniques in response to changes in temperature and pH.
Abstract: The polymorphic phase behavior of aqueous dispersions of 1-oleoyl-, 1-linoleoyl-, and 1 - linolenoyl-sn-3-glycerophosphoethanolamine ( 1 -C 18: l,-PE, 1 -C 18:2,-PE, and 1 -C 18:3,-PE, respectively) has been investigated by 31P NMR, small-angle and wide-angle X-ray diffraction, and freeze-fracture techniques in response to changes in temperature and pH. Between -20 and 0 "C at pH 7, NMR and X-ray data indicate that 1-C18:lC-PE adopts a lamellar phase. Above 20 OC, the X-ray diffraction from 1-C18:lC-PE reveals no long-range lattice order, whereas the NMR data indicate lamellar structure to 90 OC. Freeze-fracture electron microscopy shows that 1-C18: 1,-PE at pH 8.2 forms closed multilamellar vesicles upon dispersion and also that large unilamellar vesicles produced by extrusion techniques (LUVETs) can be made from 1-C18:lC-PE at pH 7. Such LUVETs can trap (3H)inulin and support a K+ diffusion potential for up to 4 h. At pH 8.5 and above, 1-C18:lC-PE forms optically clear, fluid dispersions with NMR and X-ray characteristics consistent with a micellar (noninverted) phase structure. Attempts to prepare LUVETs from 1-C18:lC-PE at pH 9 result in structures that can neither trap (3H)inulin nor support a membrane potential. At temperatures below -10 OC at pH 7, both 1-C18:2,-PE and l-C18:3,-PE form a lamellar phase whereas at temperatures of 20 OC and above, both lipids form optically clear, gellacious phases with NMR and X-ray characteristics consistent with a phase (such as inverted micellar) in which the phospholipid head groups are not in intimate contact with the bulk aqueous phase. For both l-C18:2,-PE and 1-C18:3,-PE at 0 OC, there is X-ray and NMR evidence, respectively, of a hexagonal phase, putatively HII, occurring as an intermediate in the lamellar-inverted phase transition.
TL;DR: The ability of LAA to prolong PTT values can be inhibited by the presence of hexagonal phase (but not bilayer phase) phosphatidyiethanolamine (PE), which indicates an ability of these antibodies to distinguish between different structural configurations of the same chemical species of phospholipid.
Abstract: Antibodies to phospholipids represent a group of poorly characterized antibodies that may have important physiological and biological functions.' The mechanism(s) responsible for the production of these autoantibodies remains unknown. One possible mechanism for the induction and/or pathogenesis of these antibodies involves alterations in the phospholipid architecture of the cell membrane. Such an explanation would seem plausible in light of the ability of membrane lipids to assume a variety of structures in addition to the bilayer phase.2 This possibility requires a clear demonstration that antiphospholipid antibodies exist that are able to distinguish different polymorphic forms of the same lipid. Our approach to this problem has involved the use of human hybridoma lupus anticoagulant antibodies (LAA) derived from patients with SLE. LAAs are antiphospholipid antibodies3 that are defined by their ability to prolong the normal clotting time in in vitro coagulation assays measuring the partial thromboplastin time (PTT). In this study, we show that the ability of LAA to prolong PTT values can be inhibited by the presence of hexagonal phase (but not bilayer phase) phosphatidyiethanolamine (PE). This finding indicates an ability of these antibodies to distinguish between different structural configurations of the same chemical species of phospholipid.