Abstract: The present invention relates to the production of lipid vesicles having a moderately volatile material such as a perfluorocarbon or a silicone oil encapsulated therein. In another aspect, lipid vesicles having a gas-filled center or core are made. The lipid vesicles having gas-filled central core are made by dehydrating vesicles having the moderately volatile liquid encapsulated in the central core. This drives off the water first, allowing the moderately volatile liquid to stabilize the vesicle structure as it dries, finally forming a central void which can refract light. The preferred vesicles of the invention are paucilamellar vesicles.

Abstract: The present invention provides for novel homogeneous immunoassay systems involving complement-mediated lysis of marker-encapsulating lipid vesicles (liposomes) for detection of analyte in a fluid sample. These systems do not require the separation of unbound antigens and/or antibody conjugates yet provide highly sensitive procedures for analyte detection. Liposomes containing a marker, are coupled to antibody fragments in a way which confers the liposomes with immunological specificity yet avoids sensitizing the liposomes to complement mediated lysis in the absence of analyte. Antibody sensitized liposomes (the first reagent) are sequentially incubated with an analyte-containing sample, and optionally "dummy" liposomes, which do not contain encapsulated marker, a second antibody (the second reagent), and finally with a complement source such as plasma. Complement is activated by the liposome-antibody-antigen-second antibody complex causing liposome lysis and a concomitant release of marker.

Abstract: Methods are described for controlling the transbilayer distribution of ionizable lipids and proteins in vesicles. Control of the ion gradient of the exterior bathing medium in relation to that of the interior entrapped aqueous compartment of the vesicles induces migration of ionizable lipids or proteins to one or the other of the monolayers comprising the bilayer. This can result in an asymmetric distribution of the ionizable lipid or ionizable protein. The basic ionizable lipids, such as stearylamine and sphingosine, are sequestered into the inner monolayer when the liposome interior is acidic relative to the liposome exterior. Conversely, acidic ionizable lipids such as oleic acid and stearic acid are sequestered into the inner monolayer when the liposome interior is basic relative to the liposome exterior bathing solution.

Abstract: Cosmetic or pharmaceutical composition consisting of a dispersion in a physiologically acceptable aqueous phase D of vesicles of ionic and/or nonionic amphiphilic lipid(s), the vesicles being bounded by one or more lipid lamellae, the lipid lamellae containing at least one retinoid compound and the aqueous dispersion phase a pyrimidine derivative. The said composition may be used by topical application on the hair and scalp.

Abstract: An improved simple, efficient, safe, economical, and fast transmembrane loading procedure for efficient active loading of weak amphiphatic drugs into liposomes using the transmenbrane gradient. The resulting liposomes loaded with the amphiphatic drug are stable and safe. A storageable form of loadable liposomes has extended period of stability. The reversed procedure is applicable for sustained release of liposome encapsulated drugs from ammonium liposomes.

Abstract: A surface-modifiable liposome comprising a compound represented by formula (I) or (II): ##STR1## and a lipid capable of forming a liposome, wherein R.sub.1 represents a hydrophobic group;R.sub.2 and R.sub.3 represent each an organic group including a hydrogen atom) R.sub.2 and R.sub.3 optionally combined with each other to form a double bond or a ring;X and Y each represents an oxygen atom or a sulfur atom; R.sub.2 ' and R.sub.3 ' each represents a hydrogen atom or an organic group; W represents a linking group; n represents 0 or 1; and Z represents a hydrophilic group;and a process for producing a surface-modified liposome by using the surface-modifiable liposome.

Abstract: The present invention relates to a system and to a method of delivering a drug to a preselected target body site of a patient, comprising the steps of encapsulating the chemical agent within liposomes, essentially temperature insensitive, i.e. not having a specific predetermined phase transition temperature within the specific temperature range of drug administration; administering the liposomes to the target body site; and subjecting the target body site to nonionizing electromagnetic fields in an area of the preselected target body in order to release said chemical agent from the liposomes at a temperature of between about +10 and 65.degree. C. The invention further relates to the use of said liposomes to bind to the surface of or to enter target tissue or an organ in a living system, and, when subjected to a nonionizing field, to release a drug from the liposomes into the target site.

Abstract: An improved, rapid method for preparing substantially spherical multilamellar liposomes of a defined and adjustable size within the range of 2 to 100 micrometers, suitable for encapsulation and targeting of drugs.

Abstract: A liposome immunoassay comprising the steps of reacting an analyte antigen, a liposome bearing antibody comprising a first antibody to the analyte antigen and a liposome encapsulating a marker therein linked to the antibody, and a second antibody to the analyte antigen to form an antigen-antibody complex, releasing the marker from the liposome in an amount depending on an amount of the analyte antigen in the presence of a complement, and measuring the released marker to determine the analyte antigen, characterized in using a third antibody capable of binding directly or indirectly to the second antibody and having an ability to activate the complement; andA kit for liposome immunoassay comprising at least one of; (1) an liposome bearing antibody comprising a first antibody to an analyte antigen and liposome encapsulating a marker therein linked to the antibody; (2) a second antibody to the analyte antigen; (3) a third antibody capable of binding directly or indirectly to the second antibody and having an abil

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.

Abstract: A photoresponsive liposome which comprises a compound represented by the following general formula (I): ##STR1## wherein R.sub.1 is an alkyl group; R.sub.2, R.sub.3, R.sub.4 and R.sub.5, which may be the same or different, are selected from the group consisting of an alkyl group, a substituted alkyl group, an alkoxy group, a substituted alkoxy group, a halogen atom and a hydrogen atom; R.sub.6 and R.sub.7, which may be the same or different, are an alkyl group or a hydrogen atom; n is an integer of 1 to 2; and X represents a hydrophilic group, a hydrophobic group or a combination of hydrophilic and hydrophobic groups, bonded through a connecting group, provided that any of these hydrophilic and hydrophobic groups has such properties that the compound represented by the general formula (I) becomes available as a component forming the membrane of liposome.

Abstract: The formation of spontaneous, thermodynamically stable vesicles from surfactant solutions is described. The vesicles comprise at least one single-chain, anionic surfactant and at least one single-chain cationic surfactant. Use of the vesicles in ultrafiltration treatment of water is disclosed.

Abstract: This invention relates to the identification of verocytotoxin receptors of the formula:X--O--Y(R) (I)wherein Y is sphingosine, hydroxylated sphinogosine or saturated sphingosine,wherein X is selected from said group and optionally a polysaccharide linking X to the --O--Y(R) group, andwherein R is H, or a fatty acid and R is linked to the amine moiety of the sphingosine,in combination with an assay component and their use in novel receptor-binding assays for the detection and quantitation of verocytotoxins.

Abstract: A method for rapidly lysing liposomes having transition temperatures in the range of 35.degree. C. to 65.degree. C. is provided. Such liposomes are treated with a surfactant including polyethyleneglycol mono-n-alkyl ethers such as C.sub.12 H.sub.25 O(CH.sub.2 CH.sub.2 O).sub.n H where n=9-10, a nine mole ethylene oxide adduct of a blend of n-dodecanol, n-tetradecanol and n-hexadecanol, or other appropriate polyethyleneglycol mono-n-alkyl ether capable of causing rapid lysis. The method is applicable to fluorescence immunoassay procedures.

Abstract: The invention relates to a .sup.99m Tc-labeled liposome encapsulated protein and to a highly efficient method of radiolabeling liposome encapsulated protein. In particular, a .sup.99m Tc carrier is used to label preformed liposome-encapsulated hemoglobin. The liposome-encapsulated .sup.99m Tc labeled hemoglobin is highly stable in vitro and in vivo and is suitable for a variety of clinical uses, including biodistribution imaging studies. The invention also relates to a method of using technetium-.sup.99m labeled liposome encapsulated hemoglobin to label neutrophils. A kit method which could be used for the convenient preparation of .sup.99m Tc-labeled liposome encapsulated hemoglobin for clinical use is also disclosed.

Abstract: Diagnosis of Lyme disease by immunoassay for anti-Borrelia burgdorferi antibodies in the serum of a patient includes adsorption of crossreactive antibodies in the serum with antigen of Acinetobacter calcoaceticus or Treponema phagedensis prior to binding of anti-Borrelia antibodies to Borrelia burgdorferi antigen absorbed onto a solid support. The preferred assay is a flow-through assay using a porous membrane as the support and a dye-loaded liposome conjugated to a goat antihuman antibody for detection. The invention includes a kit of materials for performing the assay.

Abstract: A pharmacological agent-lipid solution preparation comprising a lipophilic pharmacological agent, a desalted charged lipid and an aqueous-miscible lipid solvent such that upon introduction into an aqueous medium a suspension of lipid aggregates associated with the pharmacological agent are formed, and methods of manufacture and use.

Abstract: A method and product for preparing a controlled-release composition are provided. The method comprises formation of a mixture containing at least one amphiphilic substance capable of forming a liquid crystalline phase, in contact with a liquid selected from the group consisting of water, glycerol, ethylene glycol, propylene glycol and mixtures thereof. The method includes a step of providing in such mixture a bioactive material. Preferred controlled-release compositions include an alkylbetaine zwitterionic surfactant therein.

Abstract: A new method of producing paucilamellar lipid vesicles has been developed. The vesicles are made of non-phospholipid surfactants. The paucilamellar lipid vesicles have 2-8 lipid bilayers surrounding a central cavity which may be filled with either an aqueous-based solution or an oil or wax.

Abstract: Physically and chemically latentiated autobiotics are described. The latentiated autobiotics are useful for the treatment or prevention of any disease or condition, which results from the presence of nonself cells in a vertebrate host. Latentiated autobiotics are furthermore useful in suppressing immune rejection processes, as radiosensitizers and as anticoagulants.

Abstract: Lipid membrane structures containing, in the lipid membrane thereof, a compound represented by formula (I): ##STR1## wherein R.sub.1 represents a hydrogen atom or a fatty acid residue; R.sub.2 represents a hydrogen atom or an acyclic hydrocarbon residue; R.sub.3 represents an amino group, a guanidino group or an amidino group; and n represents an integer of from 1 to 6; provided that R.sub.1 and R.sub.2 do not represent hydrogen atoms at the same time, or a salt thereof. The lipid membrane structures exhibit excellent specific affinity for tumor cells and can be delivered preferentially to tumor cells.

Abstract: A reconstituted high density lipoprotein containing particle is disclosed. The particle is useful in removing excess lipid soluble material from a subject to which it is administered, as well as in delivery of lipid soluble pharmaceuticals to subjects or patients.

Abstract: Microcapsule-reagents are prepared by previously reacting at least a part of an antigen or antibody attached to microcapsules encapsulating a labeling substance with an antibody or antigen which is specifically reactive therewith, and then the reagent thus prepared is reacted with a sample containing an antigen or antibody in the presence of a complement, whereby highly sensitive immunoassay of the antigen or antibody in the sample can be realized even when the antigen or antibody attached to the microcapsules has a lowered activity or has only low reactivity with the antibody or antigen in the sample.

Abstract: There is disclosed, in an immunoassay employing an immunoassay reagent comprising liposomes comprised of at least any one of phospholipids and glycolipids, a marker material enclosed in said liposomes, and an antibody or part of the antibody, or an antigen, immobilized on said liposomes by a cross-linking method, the improvement wherein a material for preventing nonspecific lysis of the liposomes is made present together in a reaction mixture.

Abstract: This application describes the preparation and in vivo testing of surface coatings and matrix materials, which when applied to or caused to comprise the carriers for drugs and diagnostic agents, and administered in a fashion that allows efficient vascular access, causes the carriers to recognize determinants present or normal or focally diseased endothelium, and induces the following in vivo effects: 1) rapid, partial or total endothelial envelopment of the drug (diagnostic) carrier; 2) sequestration of the carrier and protecting entrapped agent from blood vascular clearance at an early time (2 minutes) when the endothelial pocket which envelops the carrier still invaginates into the vascular compartment; 3) acceleration of the carrier's transport across or through the vascular endothelium and/or subendothelial structures into the tissue compartment (interstitium); and 4) improvement of the efficiency with which the drug (or diagnostic) carrier migrates across the endothelium, or epi-endothelial or subendothe

Abstract: Disclosed are paucilamellar lipid vesicles reinforced with polyacrylamide, and methods of producing the same. The vesicles include about 2-10 lipid bilayers in the form of substantially spherical shells separated by a plurality of aqueous layers. Each of the bilayers have a layer of polyacrylamide lining its innermost side. The bilayers and the aqueous layers surround a large, substantially amorphous central cavity containing a water-immiscible oily phase or a polyacrylamide core.

Abstract: The present invention relates to a process for forming stable, uniform unilamellar or oligolamellar liposomes which encapsulate a macromolecule. However, unlike prior processes, the present method maintains a temperature below the phase transition temperature of the lipid used to make the liposome both during the hydration of the lipid and, if used, during an extrusion step. In addition, the liposome is formed and the macromolecule encapsulated in a low ionic strength solution, then they are dialyzed against a high ionic strength solution.

Abstract: A method for releasing encapsulated marker molecules from within liposomes comprises contracting the liposomes with an effective amount of a water-miscible alcohol. The chemiluminescence of acridinium esters is enhanced by oxidizing the acridinium ester in the presence of an effective amount of a water-miscible alcohol.

Abstract: In the presence of a preserving additive, unilamellar phospholipid vesicle preparations are preserved during dehydration. Dehydration is effected by subjecting said preparations to a drying operations capable of causing flash evaporation.

Abstract: Liposomes suitable as ultrasound contrast agents which contain media of various types including gases, gaseous precursors activated by pH, temperature or pressure, as well as other solid or liquid contrast enhancing agents, are described. Methods of using the same as ultrasound contrast agents are also disclosed. The present invention also comprises novel methods for synthesizing liposomes having encapsulated therein gases.

Abstract: A liposome composition and methods for making same are disclosed, such compositions comprise an arachidonic acid metabolite such as a prostaglandin, preferably prostaglandin E.sub.1, a lipid, and a drying protectant such as a saccharide. The liposomes may be loaded with prostaglandin passively, or using a transmembrane concentration gradient, preferably using a transmembrane pH gradient. Using this transmembrane loading technique, trapping efficiencies of 50% to 100% are achieved, and the release rate of the prostaglandin from the liposomes is reduced. The liposome size is maintained after lyophilization and reconstitution.

Abstract: Liposome and lipidic particle formulations of compounds are prepared by dissolving in a solution of liposome-forming lipids in an aprotic solvent such as DMSO, optionally containing a lipid-solubilizing amount of a lower alkanol, and injecting the resulting solution into an aqueous solution. The resulting liposome or lipidic particle suspension may then be dialyzed or otherwise concentrated. This method is particularly useful for compounds which are poorly-soluble in aqueous solution, but is generally useful for any compound or combination of compounds which can be dissolved in the aprotic solvent or aprotic solvent/lower alkanol mixture.

Abstract: Methods for encapsulating ionizable antineoplastic agents in liposomes using transmembrane potentials are provided. Trapping efficiencies approaching 100% and rapid loading are readily achieved. Dehydration protocols which allow liposomes to be conveniently used in the administration of antineoplastic agents in a clinical setting are also provided. In accordance with other aspects of the invention, transmembrane potentials are used to reduce the rate of release of ionizable drugs from liposomes.

Abstract: Assay methods and compositions are provided for determining an analyte in a sample suspected of containing the analyte. The composition comprises in a novel single liquid reagent at least one specific binding pair (sbp) member and its complementary member wherein at least one sbp member is reversibly confined in a material that temporarily renders the confined sbp member incapable of binding with its complementary sbp member. At least one of the sbp members is bound to a member of a signal producing system capable of producing a detectable signal in relation to the amount of analyte in the sample. The confinement is reversed, any remaining members of the signal producing system are added, and the signal produced in relation to the amount of analyte is measured. Examples of the confining material are lipid bilayers, cells and gels.

Abstract: Phospholipid conjugate compounds derived from cardiac glycosides and steroids useful in liposome immunoassays are disclosed as well as their method of preparation.

Abstract: Osmotically derived liposomal vesicles loaded with an active agent are disclosed. Liposomes, including an entrapped osmotic agent, are contacted one or more times with a washing solution which is hypotonic to the entrapped osmotic agent and which contains active agent. The entrapped osmotic agent in the liposome and the active agent in the washing solution are each present in concentrations causing the liposomes to swell, rupture under osmotic pressure, spill osmotic agent into the washing solution and re-form to encapsulate active agent.

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.This is a divisional application of copending application Ser. No. 941,913, filed Dec. 15, 1986, which is now U.S. Pat. No. 4,885,172, which is a continuation-in-part of copending application Ser. No. 811,037, which in turn is a continuation-in-part of copending application Ser. No. 749,161, filed June 26, 1985, both now abandoned and copending application Ser. No. 759,419, filed July 26, 1985 now U.S. Pat. No. 4,870,635.

Abstract: Sacs comprising a compound having a hydrophilic peptide radical are prepared and are believed to have improved stability as a result of hydrogen bonding. The sacs, including a detectable marker and derivatized with a ligand may be used as a tracer in an assay.At least a portion of the sac is formed from a compound having the following structural formula:X-Y-Z,whereinX is a hydrophobic radical;Y is a hydrophilic peptide; andZ is a radical which includes a non-hydrolyzable polar group.

Abstract: Small unilamellar liposomes (d<600 nm) comprising an unsaturated phosphatidylethanolamine (PE) such as dioleoyl PE (DOPE) and a fatty acid such as oleic acid (OA) are stabilized by adding to a freshly prepared liposome suspension, an amphipile which has a high tendency to form micelles. Examples are shown for the following micelle-forming amphiphiles: lysophospholipide, gangliosides (GM.sub.1 and GTlb), sulfatide, synthetic glycopholipids such as sialo-lactosyl phosphatidylethanolamine, liopohilic drugs such as cytosine arabinoside diphosphate diacyglycerol, and proteins such as cytochrome b.sub.5, human high density lipoprotein (HDL), and human glycophorin A. The stabilized liposomes are resistant to the lytic action of albumin, the major blood component which causes the lysis of this type of liposome. Prior to the present invention, liposomes comprising PE and OA were typically stabilized by the incorporation of cholesterol.

Abstract: Formulations consisting of phospholipid small unilamellar particles encapsulating polyene antifungal antibiotics and methods for using such compositions to treat systemic fungal infections are described. In a preferred embodiment, the particles are in the form of vesicles which comprise a polyene antifungal antibiotic, preferably amphotericin B and/or nystatin, egg phosphatidylcholine and cholesterol, preferably in the molar ratio of about 0.2 (AMB):2(PL):1(CHOL). These vesicles may also have an amine modified surface. The vesicles are suspended in a low ionic strength saccharide/tris solution at a pH of from about 6.0 to about 8.0 and may be administered to deliver the anti-fungal antibiotic to treat systemic fungal infections.

Abstract: Methods and compositions are described for the preparation of alpha-tocopherol vesicles, the bilayers of which comprise a salt form of an organic acid derivative of alpha-tocopherol such as the Tris salt form of alpha-tocopherol hemisuccinate. The method is rapid and efficient and does not require the use of organic solvents. The alpha-tocopherol vesicles may be used to entrap compounds which are insoluble in aqueous solutions. Such preparations are especially useful for entrapping bioactive agents of limited solubility, thus enabling administration in vivo.

Abstract: This invention relates to a composition comprising hydrous lipidic lamellar phases or liposomes containing, as an active agent a retinoid or a structural analogue of retinoid, such as a carotenoid or tretinoin. These compositions are more efficient against acne and less irritant for the skin and they are used as a pharmaceutical composition, notably dermatological or cosmetic.

Abstract: Disclosed are paucilamellar lipid vesicles made of single chain nonphospholipid anionic or zwitterionic surfactants and a method of their manufacture. The preferred vesicle forming materials are single chain sarcosinamides having 12-20 carbon chains and single chain betaines. The vesicles are formed rapidly and can be used to encapsulate aqueous or oily solutions.

Abstract: A process for producing a dispersion of spherules of a lipid compound encapsulating an aqueous phase includes admixing a water-dispersible lipid compound with an aqueous phase to be encapsulated in the spherules, agitating the resulting mixture to form a lamellar phase, adding a liquid dispersion phase and vigorously shaking the resulting mixture.

Abstract: A method is provided for delivering micellular particles containing a radiolabelled marker to tumors within humans. The micellular particles are less than approximately 2000.ANG. and incorporate essentially chemically pure phospholipid molecules in their external surface. Human patients given intravenous injections of such radiolabelled micellular particles showed tumors imaged by such method, without developing symptoms related to the micellular particles.

Abstract: This invention relates to a flotation immunoassay employing a novel buoyant matrix to which an antigen or antibody is coupled and which separates the bound and free products of the assay by floating to the surface of the reaction liquid. The novel flotation device which makes it possible to detect and to quantitate either antigen or antibody can also be used to fractionate cells and molecules.

Abstract: A dispersion of a uniformly sized population of multilamellar lipid vesicles (liposomes) encapsulating an aqueous liquid is prepared by forming a dried film of lipids on the walls of a vessel, contacting the film with an aqueous liquid in the presence of spherical contact masses such as glass beads and agitating. The liposomes have mean diameters in the range of about 150 to about 3000 nanometers and the contact masses have mean diameters of about 50 to 3,000 microns. The aqueous liquid encapsulated may contain enzymes, drugs or marker substances such as colorimetric or fluorescent dyes. A member of a immunological binding pair may be associated with the surfaces of the liposomes for carrying out immunoassays. This method allows for the use of small quantities of marker and lipid, leaves no residual solvents, allows for contact with only glass surfaces and involves no transfer of liposome preparations from lipid film drying vessels to sizing apparatus.

Abstract: The present invention relates to an aerosol composition for in vivo imaging or ex vivo diagnosis of tumors, which composition contains one or more soluble fragments of bacterial wall or cell peptidoglycan or equivalent synthetic compounds which are labelled with a radioactive, paramagnetic or fluorescent element and encapsulated in liposomes and a substrate which can be used for administration by aerosol.

Abstract: A method for reducing the lamellarity of a population of liposomes is provided which comprises repeatedly passing the liposomes under pressure through a filter which has a pore size equal to or less than about 100 nm. In certain embodiments, the method is used to convert a population of previously formed multilamellar liposomes into a population of substantially unilamellar liposomes. In accordance with other aspects of the disclosure, liposomes are prepared directly from a lipid powder or pellet and buffer without the use of any solvents, detergents or other extraneous materials.

Abstract: The present invention relates to a process of stabilizing micellular particles such as vesicles and increasing the shelf life by suspending the particles in a polymeric gel matrix. The invention also relates to such particles suspended in the gel matrix with a protective gel surface thereabout which is capable of becoming fluid and converting the protective surface of an aqueous suspension.