Abstract: A method for encapsulation of antineoplastic agents in liposomes is provided, having preferably a high drug:lipid ratio. Liposomes may be made by a process that loads the drug by an active mechanism using a transmembrane ion gradient, preferably a tranamembrane pH gradient. Using this technique, trapping efficiencies approach 100%, and liposomes may be loaded with drug immediately prior to use, eliminating stability problem related to drug retention in the liposomes. Drug:lipid ratios employed are about 3-80 fold higher than for traditional liposome preparations, and the release rate of the drug from the liposomes is reduced. An assay method to determine free antineoplastic agents in a liposome preparation is also disclosed.

Abstract: The present invention encompasses membranous baculovirus-derived vesicle compositions having exposed on their external surfaces a ligator capable of selectively binding a ligand to be detected. The compositions also have exposed on their outer surfaces a signal reagent capable of reacting with another signal reagent to generate a signal capable of being detected. The present invention also encompasses assay methods for determining the presence and amount of a ligand in a sample using the membranous vesicle compositions of the present invention.

Abstract: Labelling techniques for specific binding agents are provided wherein the label used comprises a microcapsule containing a nucleotide, preferably in solid form and preferably in crystalline form. Preferred nucleotide is ATP. The presence of labelled agent is determined by disrupting the microcapsule and measuring the amount of nucleotide so released; that being related to the amount of binding agent and thus any related interaction with the target for that agent such as a specific DNA or microorganism.

Abstract: Methods of increasing the circulation half-life of protein-based therapeutics in a host, the methods comprising: (a) administering to the host an amount of a first liposome formulation comprising liposomes and an antineoplastic agent; and (b) administering to the host a second formulation comprising the protein-based therapeutic, wherein the amount of the first liposome formulation is sufficient to suppress an immune response to the protein-based therapeutic of the second formulation, thereby increasing the circulation half-life of the protein-based therapeutic.

Abstract: The invention relates to methods of salvaging a target cell from cell death, comprising contacting a target cell having a disrupted cell membrane with a specific affinity reagent-liposome conjugate in an amount effective and for a time sufficient to allow the conjugate to prevent cell death due to membrane disruption; and determining the viability of the target cell. Methods of delivering a selected agent into a damaged target cell for diagnosis and therapy are also disclosed.

Abstract: Liposome reagents used in assays to detect the presence or amount of an analyte in a test sample, particularly where the analyte is antiphospholipid antibodies are described. The liposome reagents comprise a liposome, a ligand chosen to bind specifically with the analyte and associated with the liposome membrane, and a haptenated component associated with the membrane of the liposome where the hapten is chosen to bind specifically to a receptor bound to a solid phase or to a label compound that is an element of a signal detection system and where the liposome reagent is prepared so that during the assay the linkage between the solid phase and ligand of the liposome reagent is maintained.

Abstract: The present invention relates to the detection of a variety of analytes in a patient sample employing liposomes with associated ligand, where the ligand is capable of binding target analyte in that sample. In another aspect of the invention, the assays employ liposomes as a soluble support matrix where at least a portion of the support is associated with the ligand and the ligand is in a confirmation permitting it to bind to target analyte in a patient sample.

Abstract: A particularly efficient design for a nonbibulous lateral flow one step assay for an analyte in a biological sample is disclosed. In the improved device of the invention, three zones which are in nonbibulous lateral flow contact are employed: a sample receiving zone, a labeling zone, and a capture zone. The sample containing analyte is carried through the labeling zone and interacts with an assay label comprising visible moieties, preferably particles, which are coupled to specific binding reagent for analyte or to a competitor with analyte for a capture reagent. The flow continues into the capture zone where the visible moieties to which analyte or competitor are coupled are captured. Excess fluid is absorbed into an absorbent zone in contact with the capture zone. A positive result is obtained by visualizing the visible moieties in the capture zone.

Abstract: Therapeutic drug delivery systems comprising gas-filled microspheres comprising a therapeutic are described. Methods for employing such microspheres in therapeutic drug delivery applications are also provided. Drug delivery systems comprising gas-filled liposomes having encapsulated therein a drug are preferred. Methods of and apparatus for preparing such liposomes and methods for employing such liposomes in drug delivery applications are also disclosed.

Abstract: A particularly efficient design for a nonbibulous lateral flow one step assay for an analyte in a biological sample is disclosed. In the improved device of the invention, three zones which are in nonbibulous lateral flow contact are employed: a sample receiving zone, a labeling zone, and a capture zone. The sample containing analyte is carried through the labeling zone and interacts with an assay label comprising visible moieties, preferably particles, which are coupled to specific binding reagent for analyte or to a competitor with analyte for a capture reagent. The flow continues into the capture zone where the visible moieties to which analyte or competitor are coupled are captured. Excess fluid is absorbed into an absorbent zone in contact with the capture zone. A positive result is obtained by visualizing the visible moieties in the capture zone.

Abstract: The production of artificial viral envelopes by a novel double-detergent dialysis technique is disclosed. Specifically exemplified is the production of HIV-1 and RSV viral envelopes. The resulting artificial viral envelopes are essentially identical to the natural virus with regard to characteristics which are relevant to immunogenicity and intracellular transfer of encapsulated material.

Abstract: A multivesicular liposome composition containing at least one acid other than a hydrohalic acid and at least one biologically active substance, the vesicles having defined size distribution, adjustable average size, internal chamber size and number, provides a controlled release rate of the biologically active substance from the composition. A process for making the composition features addition of a non-hydrohalic acid effective to sustain and control the rate of release of an encapsulated biologically active substance from the vesicles at therapeutic levels in vivo.

Abstract: Liposomes containing cyclodextrin in the encapsulated aqueous phase are useful for encapsulation of biologically active substances, especially those which are hydrophilic. The encapsulated cyclodextrin facilitates a slow, controlled release of pharmacologic compounds from the liposomes. The novel methods of the present invention allow the treatment of a variety of pathophysiological states by administering the cyclodextrin-containing liposomes encapsulating the pharmacologic compounds. The present invention also provides a novel method of extending the half life of a pharmacologic compound in an animal.

Abstract: An immunoagglutination reagent includes liposomes, as a carrier, with a covalently bound antigen or antibody immobilized thereon. The reagent is used to assay an antibody or an antigen on the basis of agglutination. The assaying can be done at a high sensitivity in the short wave region where the change in turbidity caused by the agglutination is enhanced. An antibody or an antigen is immobilized onto the surface of the liposome, and a water-soluble polymer compound or a gelled compound is entrapped in the liposomes. The substance entrapped in the immunoagglutination reagent enhances the change in turbidity via the agglutination caused by the antigen-antibody reaction.

Abstract: The production of artificial viral envelopes by a novel double-detergent dialysis technique is disclosed. Specifically exemplified is the production of HIV-1 and RSV viral envelopes. The resulting artificial viral envelopes are essentially identical to the natural virus with regard to characteristics which are relevant to immunogenicity and interacellular transfer of encapsulated material.

Abstract: Antitumor vaccine compositions and methods for treating tumors that express the GA733-2 antigen are disclosed. The vaccines comprise a GS733-2 antigen in a liposomal carrier.

Abstract: Gas and gaseous precursor filled microspheres, and foams thereof, provide novel topical and subcutaneous delivery vehicles for various active ingredients, including drugs and cosmetics.

Abstract: The invention provides a method of separating liposomes or lipid complexes from a fluidic medium. The method involves passage of a fluidic medium containing liposomes or lipid complexes through a composite filter which retains the liposomes or lipid complexes while allowing the fluidic medium to pass through. The filter is composed of a ceramic membrane and a ceramic substrate that is thicker than the ceramic membrane. Moreover, the average pore size of the ceramic membrane, from about 0.1 to about 0.2 microns, is less than the average pore size of the substrate.

Abstract: Methods for labeling a material are disclosed. The methods comprise combining with the material (a) a photosensitizer capable upon irradiation of generating singlet oxygen and (b) a chemiluminescent compound capable of being activated by singlet oxygen wherein the photosensitizer and the chemiluminescent compound are incorporated in a particulate matrix or a non-particulate solid matrix. The particulate matrix can be solid or fluid. The methods allow for generating delayed luminescence, which can be realized upon irradiation of the matrix. The methods have application to the determination of an analyte in a medium suspected of containing the analyte.

Abstract: A pharmaceutical vehicle which is a nanoemulsion is formulated using 0.1-10 % (w/v) of an oil; 0.1-10% (w/v) of a non-ionic surface active agent; a maximum of 0.01% (w/v) of benzalkonium chloride; a drug or a precursor or active substance; and optionally, one or more of the following components; isotonizing agents, viscosity modifying agents, stabilizers, buffers and/or antioxidants. The vehicle is prepared by emulsification of an aqueous phase which contains a non-ionic surface active agent with an organic phase containing dissolved therein an oil and the drug, drug precursor or active substance in an organic water miscible solvent and then totally removing by evaporation the organic solvent and part of the water up to the final desired volume. The vehicle is especially useful in ophthalmic preparations used to treat eye disorders and diseases.

Abstract: Stabilized microspherical particles having hydrophobic liquid cores prepared as oil-in-water microemulsions. The particles are stabilized by a surface layer comprising an amphiphilic compound and may be functionalized to allow covalent coupling of a ligand to the surface of the particle. When used as tracers in assays, a water insoluble dye may be incorporated in the core liquid of the microparticles.

Abstract: The invention relates to an oil-in-water emulsion comprising 0.01-50% by weight of the total preparation, preferably 0.1-10%, of a galactolipid material as an emulsifier. The galactolipid material consists of at least 50% digalactosyldiacylglycerols, the remainder being other polar lipids. The said emulsion is suitable as a carrier for one or more active substances in a pharmaceutical composition, but also in nutritional, cosmetical, food and agricultural products.

Abstract: Liquid bioadhesive microemulsions or liposomic dispersions containing proteinic substances, especially calcitonin, that allow the systemic, local or topical administration of drugs by transmucosal route are described. This type of administration shows some considerable advantages of activity, tolerability, dosage individualization and drug stability. The compositions contain proteinic substances, and a polyoxyethylene-polyoxypropylene thermosetting copolymer. At body temperature the viscosity of the compositions is increased and provides increase residence time at the administration site.

Abstract: An improved liposome and related methods for using the liposome to facilitate the delivery of an extracellular agent to the cytoplasm of a target cell are provided. The improved liposomes include a phagosomal membrane permeabilizer, such as a hemolysin.

Abstract: An interaction system, including an antibody or, antibody fragment having functional capability, which comprises a surfactant-stabilized microheterogeneous dispersion of aqueous phase in a water-immiscible medium, said aqueous phase containing an amount of said antibody or said fragment in a functional state sufficient to effect the interaction; and methods for making and for using said system.

Abstract: Liposome carrier systems, methods and pharmaceutical compositions that target an organ preferentially with high concentrations of at least one therapeutic agent utilize a liposome carrier having a lipid membrane and an aqueous space to deliver pharmacologically active agents, such as free radical scavengers and antioxidants, to a target organ such as the liver. At least one free radical scavenger and/or antioxidant and a liposome carrier may be provided to a liver donor prior to harvesting to preserve the liver for transplantation.

Abstract: A cyclosporine(s)-containing pharmaceutical preparation for oral application is disclosed, comprising the following components:(a) at least one cyclosporine,(b) at least one natural oil of natural origin,(c) at least one member selected from the group consisting of 3-sn-phosphatidyl choline and phosphatidyl ethanol amine, and(d) water,with the proviso that ionic and non-ionic surfactants are excluded.

Abstract: Disclosed are hybrid paucilamellar lipid vesicles containing a phospho- or glycolipid and a nonionic, anionic, or zwitterionic surfactant in the lipid bilayers. The paucilamellar vesicles may have either an aqueous or oil-filled central cavity. A method of manufacture for these vesicles is also disclosed.

Abstract: A pharmaceutical preparation is disclosed which contains one or several cyclosporine(s) , one or several natural oils, 3-sn-phosphatidyl choline and/or phosphatidyl ethanol amine and water.

Abstract: Stabilized microspherical particles having hydrophobic liquid cores prepared as oil-in-water microemulsions. The particles are stabilized by a surface layer comprising an amphiphilic compound and may be functionalized to allow covalent coupling of a ligand to the surface of the particle. When used as tracers in assays, a water insoluble dye may be incorporated in the core liquid of the microparticles.

Abstract: A diagnostic device is provided that determines the activity of CETP by the use of a new synthesized donor particle. The method in the diagnostic device for measuring the activity of cholesteryl ester transfer protein comprises: adding a prepared sonicated particle to a buffer to form a buffered solution, adding an Intralipid emulsion to the buffered solution for the purpose of accepting the transfer of neutral lipid, adding cholesteryl ester transfer protein to the buffered solution incubating the buffered solution, and reading the fluorescence of the buffer solution to measure the activity of the cholesteryl ester transfer protein. The synthesized donor particle is representative of a high density lipoprotein and comprises a fluorescent group, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino-covalently bound to a cholesteryl ester to form a NBD-CE core, a monolayer of phospholipid that surrounds the NBD-CE core and an apolipoprotein apoA-I associated with the monolayer and an aqueous phase.

Abstract: A method for encapsulation of antineoplastic agents in liposomes is provided, having preferably a high drug:lipid ratio. Liposomes may be made by a process that loads the drug by an active mechanism using a transmembrane ion gradient, preferably a transmembrane pH gradient. Using this technique, trapping efficiencies approach 100%, and liposomes may be loaded with drug immediately prior to use, eliminating stability problems related to drug retention in the liposomes. Drug:lipid ratios employed are about 3-80 fold higher than for traditional liposome preparations, and the release rate of the drug from the liposomes is reduced. An assay method to determine free antineoplastic agents in a liposome preparation is also disclosed.

Abstract: This invention relates to tissue specific acoustically reflective oligolamellar liposomes containing internally separated bilayers and methods to make and to use the same, alone as a perfusion ultrasonic contrast agent or conjugated to a ligand for tissue-specific ultrasonic image enhancement.

Abstract: Recognizing substances, including epidermal growth factor, gelatin, collagen and hyaluronic acid, have been covalently bound to liposomal surfaces and utilized to attach liposomes onto a cellular or an extracellular matrix (ECM) target site. These "bioadhesive" liposomes offer several advantages including the mutual protection of both the drug and biological environment; an increase in drug bioavailability and retention at the target site; and improved adherence or adhesion to the designated target site.

Abstract: An improved assay of target components in a sample utilizes specific gravity-altering particles which are attached to the target components by specific antibodies. The attached specific gravity-altering particles are preferably liposomes which will buoy or sink the targets to a common level in the specimen sample when the latter has been centrifuged in a transparent tube. The liposomes can provide an accentuated and more pronounced indication of the presence of the targets in the sample due to their ability to contain many multiples of fluorescent or non-fluorescent dye molecules with minimal steric interference with the attached antibodies' binding ability.

Abstract: Stabilized microspherical particles having hydrophobic liquid cores prepared as oil-in-water microemulsions. The particles are stabilized by a surface layer comprising an amphiphilic compound and may be functionalized to allow covalent coupling of a ligand to the surface of the particle. When used as tracers in assays, a water insoluble dye may be incorporated in the core liquid of the microparticles.

Abstract: A process for preparing a purified syphilis antigen which comprises adsorbing an extract originated from Treponemda pallidum on a hydroxyapatite gel, followed by elution, while an aqueous medium is used.

Abstract: The novel therapeutic composition of matter is useful against the class of viruses possessing an outer lipid envelope. It consists of the association of a liposome and a viral receptor protein whereby the larger, receptor-carrying liposome is coated by a number of small liposomes reducing antigenicity of the complex. The size of viral particles allows them free access to the receptors. Receptor mediated fusion of the viral envelope and the larger liposome's membrane engulfs the viral core.

Abstract: A chromatographic test strip comprising a solid support having at least a first portion and a second portion with said portions being in the same plane so as to permit capillary flow communication with each other. The sample is added to the first portion. The first portion also may comprise a tracer portion having a tracer movably supported therein. The tracer consists of a visible particulate marker. In the second portion, a binder is immobilized. The test strip is useful in a variety of immunoassays.

Abstract: A method is provided for measuring the activity of cholesteryl ester transfer protein or MTP. The method comprises the steps of: adding a prepared emulsion particle to a buffer to form a buffered solution simulating physiological conditions, adding an emulsion of lipid to the buffered solution of prepared sonicated particle, adding a source of CETP or MTP to the buffered solution, adding a compound to the buffered solution for the purpose of testing the compound's effect on the neutral lipid transfer protein (CETP or MTP) activity, incubating the buffered mixture, reading the fluorescence of the solution, and calculating the effect of the compound on the emission spectra of the transfer label so transfer activity can than be accurately determined. A device that determines the activity of CETP or MTP by the use of a newly synthesized donor particle without regard to the presence of colored or otherwise interfering factors.

Abstract: Stabilized microspherical particles having hydrophobic liquid cores prepared as oil-in-water microemulsions. The particles are stabilized by a surface layer comprising an amphiphilic compound and may be functionalized to allow covalent coupling of a ligand to the surface of the particle. When used as tracers in assays, a water insoluble dye may be incorporated in the core liquid of the microparticles.

Abstract: Disclosed are heterovesicular liposomes containing substances of different biologically active compositions each encapsulated in separate chambers of the liposomes, having defined size distribution, adjustable average size, adjustable internal chamber size and number, methods of making them, and treatment of patients with them.

Abstract: A liposome composition which is effective in administering a physiologically active substance to Peyer's patches and is characterized by containing phosphatidylcholine, cholesterol and phosphatidylinositol as lipid components and having a high ability to migrate into Peyer's patches.

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 either injecting the resulting solution into an aqueous solution, or the aqueous solution into the resulting 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: A biochemical membrane encapsulated by a synthetically-derived neuraminic acid residue, to mask the surface of the membrane from recognition and removal by the scavenging RES cells of the body.

Abstract: An indirect assay for analyte employs a particle derivatized with a plurality of molecules of one or more compounds to increase assay sensitivity. In an indirect sandwich assay format, at least one of the compounds is a binder for the analyte, and the tracer is comprised of a binder for at least one of the compounds on the particle. In this manner, a plurality of tracer molecules may be indirectly bound to a single analyte molecule which is bound in a complex formed in the assay.

Abstract: A method of extruding liposomes from liposomal material comprising extruding the liposomal material through a frit, and apparatus for extrusion.

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 either injecting the resulting solution into an aqueous solution, or the aqueous solution into the resulting 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: A method is disclosed for separating a substance from a liquid medium. The method comprises combining the liquid medium containing the substance with magnetic particles under conditions for non-specific chemical binding of the magnetic particles. Thereafter, the medium is subjected to a magnetic field gradient to separate the particles from the medium. The preferred non-specific binding is achieved as the result of charge interactions between the particles usually by means of a polyionic reagent. The method of the invention has particular application to the separation of cells and microorganisms from aqueous suspensions and also to the determination of an analyte in a sample suspected of containing the analyte. The analyte is a member of a specific binding pair (sbp). The sample is combined in an assay medium with magnetic particles and a sbp member complementary to the analyte.

Abstract: A cyclosporine(s)-containing pharmaceutical preparation for oral application is disclosed, comprising the following components:(a) at least one cyclosporine,(b) at least one natural oil of natural origin,(c) at least one member selected from the group consisting of 3-sn-phosphatidyl choline and phosphatidyl ethanol amine, and(d) water, with the proviso that ionic and non-ionic surfactants are excluded.