Abstract: A liposome preparation is provided. This liposome preparation is capable of stably encapsulating a drug which is unstable under an acidic condition, and such stable encapsulation is realized without detracting the effect realized by the modification of the membrane by a hydrophilic macromolecule such as stability in blood. More specifically, the liposome preparation comprises a unilamellar vesicle formed from a lipid bilayer comprising a phospholipid as its main membrane component, and an interior aqueous phase of the vesicle at a pH of up to 5. The liposome has a drug loaded therein, and the vesicle is modified with a hydrophilic macromolecule only on its exterior surface.

Abstract: A method and apparatus of treating tissue adjacent a bodily conduit using thermotherapy, while preventing obstructions of the bodily conduit due to edema, includes injection of a drug-encapsulated within a heat-sensitive carrier, such as a liposome, within a region of tissue to be treated. The heat produced by the energy-emitting source heats a portion of the tissue surrounding the bodily conduit to a temperature of approximately 43° C. for a time sufficient to destroy the heated portion of the tissue. In addition, the heat produced by the energy-emitting source activates the heat-sensitive carrier to activate the release of the encapsulated drug and the drug targets the tissue to be heated. The focused energy of the energy-emitting source together with the compression acting on the target area can assist in delivering drugs to the target area so that a natural stent has a long term efficacy.

Abstract: The invention provides a water soluble complex comprising an inner core of a metal or semi-conductor nanoparticle. The nanoparticle is coated with a hydrophobic ligand, which is encapsulated in a micelle. In an aqueous medium, the micelle comprises a hydrophilic shell and a hydrophobic core, the hydrophilic shell comprising a plurality of hydrophilic moieties, the hydrophobic core comprising a plurality of hydrophobic moieties, each hydrophobic moiety comprising at least one chain, each chain comprising a minimum of 8 atoms; wherein the total number of atoms in all chains for each moiety comprises at least 24 atoms. The micelle has a minimum average diameter of approximately 5 nm and a maximum average diameter of approximately 45 nm.

Abstract: The invention provides a water soluble complex comprising an inner core of a metal or semi-conductor nanoparticle. The nanoparticle is coated with a hydrophobic ligand, which is encapsulated in a micelle. In an aqueous medium, the micelle comprises a hydrophilic shell and a hydrophobic core, the hydrophilic shell comprising a plurality of hydrophilic moieties, the hydrophobic core comprising a plurality of hydrophobic moieties, each hydrophobic moiety comprising at least one chain, each chain comprising a minimum of 8 atoms; wherein the total number of atoms in all chains for each moiety comprises at least 24 atoms. The micelle has a minimum average diameter of approximately 5 nm and a maximum average diameter of approximately 45 nm.

Abstract: Provided are a method for detecting biomaterials, a method for fabricating a chip for biomaterial detection and a chip for biomaterial detection. The method for detecting biomaterials is characterized by comprising the steps of: (S1) immobilizing polydiacetylene liposomes onto a substrate; (S2) linking the polydiacetylene liposomes together and layering them on the substrate; (S3) immobilizing a material which forms a complementary binding with a subject biomaterial to be detected onto the polydiacetylene liposomes; (S4) exposing the resulted polydiacetylene liposome to UV light so as to form a chip for biomaterial detection; (S5) applying the subject biomaterial to be detected to the chip for biomaterial detection for reaction; and (S6) measuring a fluorescent signal from the chip for biomaterial detection.

Abstract: The present invention relates to a method for making a test device for detecting or quantifying an analyte in a sample. This method involves contacting a membrane with a mixture including derivatized, marker-loaded liposomes, and substantially dehydrating the mixture on the membrane under vacuum pressure at a temperature of from about 4° C. to about 80° C., wherein said mixture further includes one or more sugars in an amount sufficient to promote the stability of the liposomes during dehydration and rehydration. The present invention also relates to a test device and method for detecting or quantifying an analyte in a sample. The test device includes a membrane which includes an immobilized liposome zone, wherein the immobilized liposome zone has bound thereto dehydrated, derivatized, marker-loaded liposomes dehydrated under vacuum pressure at a temperature of from about 4° C. to about 80° C.

Abstract: Lipid vesicle particles capable of being targeted to a cell type of interest, said particle incorporating a peptide which is responsive to a predetermined metabolic signal from the targeted cell so as to modulate the permeability of the particle, said particle further incorporating a species to be targeted to the cell which is activated on said modulation of permeability. The particles may be used in methods for detecting cells, methods of treating cells and also therapeutically.

Abstract: The present invention relates to a method for making a test device for detecting or quantifying an analyte in a sample. This method involves contacting a membrane with a mixture including derivatized, marker-loaded liposomes, and substantially dehydrating the mixture on the membrane under vacuum pressure at a temperature of from about 4° C. to about 80° C., wherein said mixture further includes one or more sugars in an amount sufficient to promote the stability of the liposomes during dehydration and rehydration. The present invention also relates to a test device and method for detecting or quantifying an analyte in a sample. The test device includes a membrane which includes an immobilized liposome zone, wherein the immobilized liposome zone has bound thereto dehydrated, derivatized, marker-loaded liposomes dehydrated under vacuum pressure at a temperature of from about 4° C. to about 80° C.

Abstract: The present invention provides a sensor surface comprising: a substrate coated with a free electron metal; and a matrix layer disposed on the free electron metal, wherein the matrix layer comprises an organic compound having a boronic acid complexing moiety. The matrix is preferably a self-assembled monolayer (SAM), a mixed self-assembled monolayer (mSAM), or combinations thereof.

Abstract: The present invention provides a method for detecting an analyte, comprising providing a sensor comprising a substrate coated with a free electron metal, a matrix layer disposed on the free electron metal, the matrix layer comprising an organic compound, wherein the organic compound has a boronic acid complexing moiety and, a boronic acid moiety complexed to the boronic acid complexing moiety; and contacting the sensor with the analyte to elicit a response; and measuring the response thereby detecting the analyte.

Abstract: The present invention herein provides the design, synthesis and characterization of compositions comprising asymmetric bolaamphiphilic lipids that form extended polymeric ribbons and wide sheets. These compositions may be doped, or interspersed, with various compounds to fine-tune the fluidity and rigidity of the bolaamphiphilic lipid composition, and promote other morphologies of the composition, including fluid vesicles and truncated flat sheets. Upon an increase in pH these compositions undergo a calorimetric and morphological transformation.

Abstract: The present invention provides prodrug and multiprodrug complexes comprising drugs specifically bound to synthetic receptors in such a manner that active drug becomes available only in the presence of a targeted pathophysiologic receptor. Methods for preparation end use of these prodrug complexes in drug delivery systems are also provided.

Abstract: Two-dimensional and three-dimensional arrays of a polydiacetylene backbone having a substrate incorporated are used in chemical sensing methods to detect the interaction of an analyte with the substrate by monitoring the change in the fluorescence of the array.

Abstract: The present invention is a self-assembling material comprised of stacks of lipid bilayers formed in a columnar structure, where the assembly process is mediated and regulated by chemical recognition events. The material, through the chemical recognition interactions, has a self-regulating system that corrects the radial size of the assembly creating a uniform diameter throughout most of the structure. The materials form and are stable in aqueous solution. These materials are useful as structural elements for the architecture of materials and components in nanotechnology, efficient light harvesting systems for optical sensing, chemical processing centers, and drug delivery vehicles.

Abstract: The invention includes a composition of matter and method that utilizes energy transfer between one or more donor and acceptor molecules. The composition of matter includes an encapsulation vesicle having a matrix, a surface coating of an organo-metallic complex and a transparent protection layer. The transparent protection layer is capable of modification by addition of biomolecules to the surface in order to bind other molecules. The proximity of the bound biomolecules to the protective layer allows for energy transfer from a donor molecule internal to the protection layer to an acceptor molecule outside the protection layer. The protection layer acts to diminish the effects of collisional quenching on the donor molecules caused by ubiquitous small molecules such as molecular oxygen. The application also teaches a method of making and applying the complexes to immunoassays.

Abstract: Particle aggregation of lipid:nucleic acid complex particles is prevented by incorporating a non-cationic lipid into lipid:nucleic acid complex particles containing a cationic lipid and a nucleic acid polymer. The non-cationic lipid is a polyethylene glycol-based polymer.

Abstract: Plasmid-lipid particles which are useful for transfection of cells in vitro or in vivo are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. The particles are typically 65-85 nm, fully encapsulate the plasmid and are serum-stable.

Abstract: Methods for detecting anti-lipidic particles antibodies and lipidic particles in cellular membranes for the diagnosis of diseases associated to the antiphospholipid syndrome are disclosed. Kits or sets to put these methods of diagnosis into practice are also disclosed. Methods for the therapeutically treatment of diseases associated to the antiphospholipid syndrome are disclosed as well. In addition, methods for the detection of the diverse physiologic states of cells, and those kits useful for this are also disclosed.

Abstract: Methods are disclosed for conjugating one moiety to another moiety. In the method the moieties are reacted with one another in a protic solvent. Reaction between the moieties and the protic solvent during the conjugating is negligible or reversible. A stable bond is formed between the moieties to produce a product that is not subject to &bgr;-elimination at elevated pH. Usually, one of the moieties comprises an unsaturation between two carbon atoms. One of the carbon atoms is or becomes an electrophile during the conjugating. The other of the moieties comprises a functionality reactive with the electrophile carbon atom to form a product that comprises the unsaturation. Compounds comprising both of the moieties as well as precursor molecules are also disclosed. Methods are also disclosed for determining an analyte in a sample employing compounds as described above.

Abstract: A process for detecting an analyte which process comprises (a) contacting a sample suspected of containing said analyte with a containment means comprising a barrier which separates signal generating reagents from said sample, in the presence of an element which interacts specifically with said analyte, under conditions whereby interaction between the analyte and the said element results in activation of the signal generating reagents within the containment means on the side of the barrier opposite to the sample, and (b) detecting any signal generated and retained within the containment means from the sample side of the barrier. The process of the invention provides for sensitive detection of very small numbers of analyte materials using measurement techniques which include counting methods such as flow cytometry.

Abstract: A method for assaying an analyte in a sample. The method comprising the steps of a) contacting the sample with material comprising a receptor which is present in a liposome and which liposome comprises a detectable functionality, said contact occurring under conditions resulting in binding of the receptor to analyte if present before or concomitant with step b, wherein step b) consists of contacting the sample with an immobilised ligand for the receptor said contact occurring under conditions resulting in binding of the receptor to the ligand, with steps a and b being followed by c) separating the resulting immobilised ligand-receptor fraction and the receptor fraction present in solution and d) assaying the detectable functionality of the receptor in a fraction from step c) in a manner known per se for its detection.

Abstract: The present application relates to a method of making liposomes having membrane proteins incorporated therein, the method comprising: providing the membrane protein in solution; providing a solution of preformed liposomes; and incubating the mixture. Prior to the step of providing a solution of preformed liposomes, the liposomes are formed by combining a mixture of phospholipids with a solution of at least one type of unsaturated fatty acid. The methods of the present invention further relate to the method of making a reagent comprising tissue factor reconstituted into preformed liposomes. The method of the present invention for making a tissue factor reagent comprises: providing tissue factor in solution; providing a solution of preformed liposomes comprising a mixture of phospholipids and at least one type of unsaturated fatty acid; and incubating the mixture.

Abstract: The invention provides heterobifunctional cross-linking reagents and methods of using the cross-linking reagents. The cross-linking reagents of the invention combine a nucleophilic hydrazide residue with an electrophilic maleimide residue allowing coupling of aldehydes to free thiols. In the methods of the invention, human immunodeficiency virus (HIV) infected cells can be detected using conjugates that include CD4 molecules conjugated to detectable markers via the disclosed cross-linking reagents.

Abstract: The present invention relates to a simple immunochemical semi-quantitative assay method according to chromatography, which comprises trapping a certain amount of an analyte in a sample with a predetermined amount of a fixed antibody for the analyte before qualitative analysis of the analyte, the certain amount corresponding to the amount of the fixed antibody, and thereby decreasing a concentration of the analyte to be subjected to subsequent immunochemical qualitative determination, and an apparatus therefor.

Abstract: Plasmid-lipid particles which are useful for transfection of cells in vitro or in vivo are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. The particles are typically 65-85 nm, fully encapsulate the plasmid and are serum-stable.

Abstract: A method for encapsulating organic molecules, and in particular, biomolecules using sol-gel chemistry. A silica sol is prepared from an aqueous alkali metal silicate solution, such as a mixture of silicon dioxide and sodium or potassium oxide in water. The pH is adjusted to a suitably low value to stabilize the sol by minimizing the rate of siloxane condensation, thereby allowing storage stability of the sol prior to gelation. The organic molecules, generally in solution, is then added with the organic molecules being encapsulated in the sol matrix. After aging, either a thin film can be prepared or a gel can be formed with the encapsulated molecules. Depending upon the acid used, pH, and other processing conditions, the gelation time can be from one minute up to several days. In the method of the present invention, no alcohols are generated as by-products during the sol-gel and encapsulation steps.

Abstract: The present invention relates to methods and compositions for the direct detection of analytes using color changes that occur in immobilized biopolymeric material in response to selective binding of analytes to their surface. In particular, the present invention provides methods and compositions related to the encapsulation of biopolymeric material into metal oxide glass using the sol-gel method.

Abstract: A method of measuring the amount of cyclosporin in a sample suspected of containing cyclosporin is disclosed. A method of inactivating interfering cross-reactive material in an assay for measuring the amount of cyclosporin in a sample suspected of containing cyclosporin is also disclosed. Compositions wherein cyclosporin is conjugated to an immunogenic carrier or a label, optionally through a linking group, at an alanine nitrogen atom of the cyclic backbone of cyclosporin are also disclosed. Compositions wherein atiocyclosporin is conjugated, optionally through a linking group, to an immunogenic carrier or a label are also disclosed. Where cyclosporin is conjugated to an immunogenic carrier, the conjugates may be used as immunogens for the preparation of antibodies which are capable of recognizing cyclosporin.

Abstract: Novel archaeosome compositions and their use in vaccine formulations as adjuvants and/or delivery systems, to enhance the immune response to immunogens in an animal such as a human, are described. Another aspect relates to the use of these archaeosomes to enhance the delivery of compounds such as pharmaceuticals to specific cell types and tissues in animals and other life forms, via various routes of administration such as subcutaneous, intramuscular, and oral. The efficacy of the archaeosomes and also of conventional liposomes can be further improved in these applications, by incorporation of coenzyme Q10 and/or polyethyleneglycol-lipid conjugate into liposomes made from these archaeosomes.

Abstract: A cartridge for separating a desired analyte from a fluid sample has a sample flow path and a lysing chamber in the sample flow path. The lysing chamber contains at least one filter for capturing cells or viruses from the sample as the sample flows through the lysing chamber. Beads are also disposed in the lysing chamber for rupturing the cells or viruses to release the analyte therefrom. An analyte flow path extends from the lysing chamber and diverges from the sample flow path. The analyte flow path preferably leads to a reaction chamber for chemically reacting and optically detecting the analyte. The cartridge also includes at least one flow controller (e.g., valves) for directing the sample into the waste chamber after the sample flows through the lysing chamber and for directing the analyte separated from the sample into the analyte flow path.

Abstract: The present invention relates to targeted polymerized liposomes for oral and/or mucosal delivery of vaccines, allergens and therapeutics. In particular, the present invention relates to polymerized liposomes which have been modified on their surface to contain a molecule or ligand which targets the polymerized liposome to a specific site or cell type. More particularly, the invention relates to the use of polymerized liposomes modified to contain a carbohydrate or lectin on their surface.

Abstract: Methods and compositions are described for the preparation of bioactive agents entrapped in lipid vesicles the bilayers of which comprise a salt form of an organic acid derivative of a sterol, such as the tris-salt form of a sterol hemisuccinate, and to bompositions comprising a mixtue of tris(hydroxymethyl)aminomethane salt of cholesteryl hemisuccinate with either an antifungal compound or a peptide. These compositions have various applications in vivo.

Abstract: Polymerized liposome particles which are linked to a targeting agent and may also be linked to a contrast enhancement agent and/or linked to or encapsulating a treatment agent. The targeting imaging enhancement polymerized liposome particles interact with biological targets holding the image enhancement agent to specific sites providing in vitro and in vivo study by magnetic resonance, radioactive, x-ray or optical imaging of the expression of molecules in cells and tissues during disease and pathology. Targeting polymerized liposomes may be linked to or encapsulate a treatment agent, such as, proteins, drugs or hormones for directed delivery to specific biological sites for treatment.

Abstract: A method of-treating a relatively aged animal to reverse age-related changes in the lipid composition of organ and tissue cells, such as heart muscle cells, and the ability of the animal to withstand respiratory stress. A suspension of small unilamellar vesicles composed predominantly of egg phosphatidyl choline is administered parenterally to the animal, preferably over a period of several days and at a dose level of between about 0.1 and 1 grams lipid per kg body weight per day. Changes in the heart muscle cells are reflected in decreased levels of serum creatine phosphokinase. Liposome administration is continued until the serum creatine phosphokinase level drops at least about 50%. Also disclosed are liposome treatment methods for increasing longevity and male fertility.

Abstract: Provided are methods for preparing improved biologically active micelle and crystalline products comprising a biologically active amphipathic compound in association with a micelle or crystalline product. Methods for producing the micelle or crystalline products as well as methods of using the micelle or crystalline products in therapeutic, diagnostic, and cosmetic, applications are also provided.

Abstract: Reagents for use in preparing a therapeutic liposome composition sensitized to a target cell are described. The reagents include a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent and a plurality of targeting conjugates composed of a lipid, a hydrophilic polymer and a targeting ligand. The therapeutic, target-cell sensitized liposome composition is formed by incubating the liposomal composition with a selected conjugate.

Abstract: This invention provides liposomes containing one or more N-acylated phosphatidylethanolamines, such liposomes being useful for localizing the delivery of bioactive agents to cells.

Abstract: Disclosed is a new structural class of amphiphilic molecules which incorporate a hydrophilic material or polymer attached, at spatially distinct sites, to at least two hydrophobic residues. Certain of the amphiphilic molecules comprise a plurality of hydrophobic moieties. All such amphiphilic molecules have a common structural motif and, in contact with water, display surface activity and self-assemble into multimolecular aggregates and liquid crystalline phases. Also disclosed are enhanced stability liposomes that incorporate such amphiphilic molecules via unique interactions, and methods of using such formulations in a variety of applications including drug delivery, nutrition, bio-diagnostics, cosmetics, blood products and related applications.

Abstract: Disclosed is a colorimetric sensor comprising polydiacetylene membrane liposomes, a polydiacetylene membrane film or fine particles coated with a polydiacetylene membrane, in which the polydiacetylene membrane is incorporated with a protein having a reduced molecular weight low enough not to cause color change in the polydiacetylene membrane. The examples of the reduced-molecular-weight proteins include an antibody Fab′ fragment, an antigenic protein of molecular weight of 100,000 or less, and a peptide consisting of 3-20 amino acid residue, which undergo an antigen-antibody reaction with an antigen or antibody contained in a sample. As the reduced-molecular-weight protein is also employed a combination of single-stranded DNA of 100 bases or less which hybridizes with single-stranded DNA contained in a sample to form a double-stranded DNA, and an antibody which reacts with said double-stranded DNA but does not react with the single-stranded DNA contained in the sample.

Abstract: The invention concerns a method for administering bioactive substances to patients at selected sites in the body and remotely promoting delivery of said media to selected organs or tissues in the body. The method comprises providing an administrable formulation comprising, dispersed in an aqueous carrier liquid, liposomes filled with bioactive substances and gas-filled microspheres, injecting said formulation into the circulation of a patient so that it is directed to a site of interest, and applying ultrasound pulses to said site so as to make the gas-filled microbodies explode and the gas confined therein to expand in the carrier liquid, the energy of expansion of said confined gas causing the liposome vesicles to open and release the trapped substances at said site.

Abstract: The present invention relates to a method for the amplification of or creation of A signalling event for detection of a probe which reacts with a test substance, the method comprising causing the test substance to react with the probe and identifying the reaction of the test substance with the probe by release of a signalling moiety from a vesicle. The invention also relates to a kit for the detection of a probe which reacts with a test substance, the kit comprising a vesicle which contains a signalling moiety.

Abstract: Methods are disclosed for determining an analyte in a medium suspected of containing the analyte. One method comprises treating a medium suspected of containing an analyte under conditions such that the analyte, if present, causes a photosensitizer and a chemiluminescent compound to come into close proximity. The photosensitizer generates singlet oxygen and activates the chemiluminescent compound when it is in close proximity. The activated chemiluminescent compound subsequently produces light. The amount of light produced is related to the amount of analyte in the medium. Preferably, at least one of the photosensitizer and chemiluminescent compound is associated with a surface which is usually a suspendible particle, and a specific binding pair member is bound thereto. Compositions and kits are also disclosed.

Abstract: A test device for detecting or determining an analyte in a test solution includes an absorbent material having separate contact, competitive binding, and measurement portions. The contact portion is positioned for contact with and uptake of the test solution. The competitive binding portion has a binding material for the analyte non-diffusively bound thereto. The measurement portion has a receptor for the analyte and marker-encapsulating liposomes non-diffusively bound thereto. In a method for using the test device, a solution containing the analyte and the analyte-liposome conjugate is allowed to traverse the absorbent material from the contact portion through the competitive binding portion and on through the measurement portion of the absorbent material. The amount of marker in the measurement portion of the absorbent material, following traversal by the test solution, is then determined as a measure of the analyte in the sample.

Abstract: The present application relates to a method of making liposomes having membrane proteins incorporated therein, the method comprising: providing the membrane protein in solution; providing a solution of preformed liposomes; and incubating the mixture. Prior to the step of providing a solution of preformed liposomes, the liposomes are formed by combining a mixture of phospholipids with a solution of at least one type of unsaturated fatty acid. The methods of the present invention further relate to the method of making a reagent comprising tissue factor reconstituted into preformed liposomes. The method of the present invention for making a tissue factor reagent comprises: providing tissue factor in solution; providing a solution of preformed liposomes comprising a mixture of phospholipids and at least one type of unsaturated fatty acid; and incubating the mixture.

Abstract: This invention relates to a fluorescence-based immunoassay method for the detection of an analyte, or for the measurement of its concentration in a biological sample. The method is based on the ability of a multivalent analyte to induce aggregation of receptor molecules labeled with a fluorophore, which molecules are anchored to and are freely mobile on a lipid membrane, and thereby cause changes in the fluorescence.

Abstract: Liposome encapsulated antibiotic therapy has limited application against infectious organisms, which can sequester in non-phagocytic cells. Virulence factors of these infectious organisms, for example bacterial components, when used in the formulation of liposomes can enhance the effectiveness of liposomes as delivery systems in the treatment of disease. In this manner, multi-functional liposomes can be developed to treat target diseases. In addition to serving as antibiotic delivery systems, such liposomes also have an immunization effect. Thus, the liposomes can be used for both the prevention and treatment of diseases.

Abstract: A method is provided for inducing a systemic immune response to an antigen selected from inactivated HIV I and HIV II antigens in a mammal. The method comprises orally administering lyophilized multilaminar liposomes containing the antigen. The liposomes have a size of from 20 nm to 20 microns. The antigen-containing liposomes are absorbed in the Peyer's patches of the gut. Sufficient antigen-containing liposomes are taken up by macrophages in the Peyer's patches to induce a systemic immune response to the antigen.

Abstract: The present invention provides compositions comprising colorimetric assay liposomes. The present invention also provides methods for producing colorimetric liposomes and calorimetric liposome assay systems. In preferred embodiments, these calorimetric liposome systems provide high levels of sensitivity through the use of dopant molecules. As these dopants allow the controlled destabilization of the liposome structure, upon exposure of the doped liposomes to analyte(s) of interest, the indicator color change is facilitated and more easily recognized.

Abstract: A direct assay is described using novel three-dimensional polymeric assemblies which change from a blue to red color when exposed to an analyte, in one case a flue virus. The assemblies are typically in the form of liposomes which can be maintained in a suspension, and show great intensity in their color changes. Their method of production is also described.

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.