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 neutral cationic lipid and liposomes prepared from the neutral cationic lipid are described. Liposomes comprised of the lipid are suitable for delivery of a polyanionic compound, such as a nucleic acid. The delivery can be performed in vivo or ex vivo. The neutral cationic lipid, which is neutral in charge at physiologic pH and positively charged at pH values less than physiologic pH, contains a polar head group that imparts solubility of the lipid and permits its packing into a liposomal lipid bilayer.

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: 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 and method for delivery of a nucleic acid in vivo or ex vivo is described. The liposomes in the composition are comprised of (i) a cationic lipid and (ii) a lipid joined to a hydrophilic polymer by a releasable linkage. The liposomes are associated with a nucleic acid for delivery to a cell.

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 compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.

Abstract: An apparatus for transdermally delivering a biologically active agent to a patient comprising a microprojection member having a plurality of microprojections that are adapted to pierce the stratum comeum of the patient, the microprojection member having a biocompatible coating disposed thereon that includes a biologically active agent selected from the group consisting of peptide and protein conjugates.

Abstract: A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.

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 for reducing complement activation upon in vivo administration of a liposome preparation containing an entrapped therapeutic agent is described. The method involves providing liposomes having a polyethylene-glycol-derived neutral lipopolymer.

Abstract: A conjugate comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-, hydroxy- or carboxyl-containing ligand is described. The resulting conjugate is capable of releasing the parent amine, hydroxy, or carboxyl-containing compound via thiol-mediated cleavage. The system allows for delivery of various amino-, hydroxy-, or carboxy-containing drugs in the form of their thiolytically cleavable macromolecular conjugates.

Abstract: A composition for delivery of Factor VIII is described.

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: A composition for delivery of Factor VIII is described.

Abstract: Methods for administering mitomycin C to a multi-drug resistant cell and for reducing the toxicity of the compound are described. In the methods, mitoymic C is provided in the form of a prodrug conjugate, where the drug is linked to a hydrophobic moiety, such as a lipid, through a cleavable dithiobenzyl linkage. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of mitomycin C in its original form. The linkage is stable under nonreducing conditions. The prodrug conjugate can be incorporated into liposomes for administration in vivo and release of mitomycin C in response to endogenous in vivo reducing conditions or in response to administration of an exogenous reducing agent.

Abstract: A composition for administration of a therapeutic compound to a multi-drug resistant cell in a person suffering from a drug-resistant cancer is described. The composition is composed of a carrier molecule and a folate targeting ligand, which is covalently attached to the carrier, and the therapeutic compound. In one preferred embodiment, the carrier is a liposome having a surface coating of hydrophilic polymer chains where a folate ligand is attached to the free distal end of at least a portion of the hydrophilic polymer chains, and the therapeutic agent is entrapped in the liposomes. The composition is effective to achieve accumulation of the therapeutic compound in the cell in an amount sufficient to be cytotoxic. Also described are methods for administering a therapeutic compound to a person suffering from a multi-drug resistant condition.

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.