Abstract: A self-contained delivery device for delivery a selected volume of stored electrolyte solution at selected time intervals is disclosed. The device includes a housing having a delivery port, a chamber containing an upstream supply reservoir for holding a quantity of electrolyte solution, a downstream delivery reservoir for receiving electrolyte solution from the supply reservoir and, disposed between the two reservoirs, a membrane having a plurality of flow-through channels extending between the two reservoirs. A pair of electrodes placed in the chamber on either side of the membrane and controlled by a controller contained within the housing for pumping selected quantities of the electrolyte solution at selected time intervals. The device includes a chamber, and a membrane disposed in said chamber and having a channel extending between an upstream chamber region, where the said channel has a selected minimum cross-sectional dimension in the range between 2 and 100 nm.

Abstract: A fusogenic liposome composition for delivering a liposome-entrapped compound into the cytoplasm of a target cell is described. The liposomes have an outer surface coating of chemically releasable hydrophilic polymer chains which shield hydrophobic polymers on the liposome outer surface. Release of the hydrophilic polymer chains exposes the hydrophobic polymers for interaction with outer cell membranes of the target cells to promote fusion of the liposome with the target cells. Also disclosed is a method for using the composition to deliver a compound to target cells, and a method for selecting suitable hydrophobic polymers for use in the composition.

Abstract: A self-contained delivery device for delivery a selected volume of stored electrolyte solution at selected time intervals is disclosed. The device includes a housing having a delivery port, and contained within the housing, a chamber containing an upstream supply reservoir for holding a quantity of electrolyte solution, a downstream delivery reservoir for receiving electrolyte solution from the supply reservoir and, disposed between the two reservoirs, a membrane having a plurality of flow-through channels extending between the two reservoirs. A pair of electrodes placed in the chamber on either side of the membrane are controlled by a controller contained within the housing, for pumping selected quantities of the electrolyte solution at selected time intervals. The invention also includes a device for detecting a target nucleic acid sequence contained in a solution of solution of nucleic acid fragments.

Abstract: A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

Abstract: A method of treating a disease or disorder characterized by angiogenic tissue growth is described. The method includes providing an immunoliposome composition comprised of (i) vesicle-forming lipids including between 1-20 mole percent of a vesicle-forming lipid derivatized with a hydrophilic polymer, (ii) a targeting ligand having biological activity to promote angiogenesis, and (iii) a drug entrapped in said liposomes; and administering the immunoliposome composition to a subject.

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: 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: The invention includes a device for detecting a target nucleic acid sequence contained in a solution of solution of nucleic acid fragments. The device includes a chamber, and a membrane disposed in said chamber and having a channel extending between an upstream chamber region, where the said channel has a selected minimum cross-sectional dimension in the range between 2 and 100 nm. Attached to a wall portion of the channel, is a capture nucleic acid having a sequence complementary to the target sequence. Upstream and downstream electrodes disposed in the upstream and downstream chamber regions, respectively, are in contact with electrolyte solution placed in the corresponding chamber regions.

Abstract: A method of liposome-based therapy for a mammalian subject is disclosed. The method uses liposomes with outer surfaces that contain an affinity moiety effective to bind specifically to a biological surface at which the therapy is aimed, and a hydrophilic polymer coating effective to shield the affinity moiety from interaction with the target surface. The hydrophilic polymer coating is made up of polymer chains covalently linked to surface lipid components in the liposomes through releasable linkages. After a desired liposome biodistribution is achieved, a releasing agent is administered to cause cleaving of a substantial portion of the releasable linkages in the liposomes, to expose the affinity agent to the target surface.

Abstract: A method of liposome-based therapy for a mammalian subject is disclosed. The method uses liposomes with outer surfaces that contain an affinity moiety effective to bind specifically to a biological surface at which the therapy is aimed, and a hydrophilic polymer coating effective to shield the affinity moiety from interaction with the target surface. The hydrophilic polymer coating is made up of polymer chains covalently linked to surface lipid components in the liposomes through releasable linkages. After a desired liposome biodistribution is achieved, a releasing agent is administered to cause cleaving of a substantial portion of the releasable linkages in the liposomes, to expose the affinity agent to the target surface.

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: A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

Abstract: A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

Abstract: Microfabricated, asymmetrical, reservoir-containing particles for use in the intravenous delivery of cytotoxic agents such as melittin to tumors is disclosed. The particles have a selected shape and uniform dimensions preferably in the 1 &mgr;m to 10 &mgr;m range. The reservoirs open to the face of the particle and are filled with a solution or suspension of the therapeutic agent and selected excipients. The drug/excipient solution may be dried by standard techniques. The excipients are selected to delay the dissolution/release of the agent from the particle reservoirs for 1-48 hours after the particle suspension is rehydrated and injected. Alternatively, the pore is plugged with an erodable material or covered with a semipermeable membrane. The face of the particle is grafted with a layer of specific ligands designed to quickly bind the particle to the surface of either tumor cells or the vascular endothelial cells, which form tumor capillaries.

Abstract: A liposome composition for localizing an anti-tumor compound to a solid tumor via the bloodstream. The liposomes, which contain the agent in entrapped form, are composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivatized with hydrophilic biocompatible polymer, and have sizes in a selected size range between 0.07 and 0.12 microns. After intravenous administration, the liposomes are taken up by the tumor within 24-48 hours, for site-specific release of entrapped compound into the tumor. In one composition for use in treating a solid tumor, the compound is an anthracycline antibiotic drug which is entrapped in the liposomes at a concentration of greater than about 50 &mgr;g agent/&mgr;mole liposome lipid. The method results in regression of solid colon and breast carcinomas which are refractory to anthracycline antibiotic drugs administered in free form or entrapped in conventional liposomes.

Abstract: A drug delivery device that includes a capsule for implantation into the body; the capsule further includes a reservoir for containing a substance such as a therapeutic agent, at least one port for allowing the substance to diffuse from or otherwise exit the reservoir, and a nanopore membrane in communication with the capsule at or near the exit port for controlling the rate of diffusion of the substance from the exit port. The device also includes an optional screen for providing structural stability to the nanopore membrane and for keeping the pores of the nanopore membrane clear. One embodiment of the drug delivery device includes an osmotic engine internal to the device for creating fluid flow through the device.

Abstract: A self-contained delivery device for delivery a selected volume of stored electrolyte solution at selected time intervals is disclosed. The device includes a housing having a delivery port, and contained within the housing, a chamber containing an upstream supply reservoir for holding a quantity of electrolyte solution, a downstream delivery reservoir for receiving electrolyte solution from the supply reservoir and, disposed between the two reservoirs, a membrane having a plurality of flow-through channels extending between the two reservoirs. A pair of electrodes placed in the chamber on either side of the membrane are controlled by a controller contained within the housing, for pumping selected quantities of the electrolyte solution at selected time intervals. The invention also includes a device for detecting a target nucleic acid sequence contained in a solution of solution of nucleic acid fragments.

Abstract: A fusogenic liposome composition for delivering a liposome-entrapped compound into the cytoplasm of a target cell is described. The liposomes have an outer surface coating of chemically releasable hydrophilic polymer chains which shield hydrophobic polymers on the liposome outer surface. Release of the hydrophilic polymer chains exposes the hydrophobic polymers for interaction with outer cell membranes of the target cells to promote fusion of the liposome with the target cells. Also disclosed is a method for using the composition to deliver a compound to target cells, and a method for selecting suitable hydrophobic polymers for use in the composition.

Abstract: A method of liposome-based therapy for a mammalian subject is disclosed. The method uses liposomes with outer surfaces that contain an affinity moiety effective to bind specifically to a biological surface at which the therapy is aimed, and a hydrophilic polymer coating effective to shield the affinity moiety from interaction with the target surface. The hydrophilic polymer coating is made up of polymer chains covalently linked to surface lipid components in the liposomes through releasable linkages. After a desired liposome biodistribution is achieved, a releasing agent is administered to cause cleaving of a substantial portion of the releasable linkages in the liposomes, to expose the affinity agent to the target surface.

Abstract: Microfabricated, asymmetrical, reservoir-containing particles for use in the oral delivery of biopolymer therapeutic agents such as peptides, proteins and oligonucleotides are disclosed. The particles are encapsulated in enteric-coated capsules or tablets to provide passage through the stomach and release of a suspension of the particles in the intestinal lumen. The particles have a selected shape, and uniform dimensions preferably in the 100 &mgr;m to 1 mm range. The reservoirs open to the face of the particle and are filled with a therapeutic agent and selected excipients. The excipients are selected to delay the dissolution/release of the agent from the particle reservoirs for 5-60 minutes after the particle is released in the intestinal lumen. Alternatively, the pore is plugged with an erodable material.