Abstract: The present invention relates to the use of copper ions to achieve enhanced retention of a therapeutic agent within a liposome. The invention may be employed to more effectively deliver a liposomally encapsulated therapeutic agent to a target site in vitro and in vivo for anti-cancer or other therapy. The liposome may comprise an interior buffer solution containing the therapeutic agent, the solution having a pH less than 6.5 and most preferably approximating pH 3.5. At least some of the copper ions are retained within the interior solution. In a particular embodiment the therapeutic agent may be a chemotherapeutic drug, such as irinotecan. The invention may also comprise an ionophore to facilitate loading of drug into the liposome. In one particular embodiment the combination of the ionophore A23187 and encapsulated divalent copper (Cu2+) resulted in an irinotecan formulation that exhibited surprisingly improved drug retention attributes.

Abstract: Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

Abstract: Compositions which comprise delivery vehicles having stably associated therewith non-antagonistic combinations of two or more agents, such as antineoplastic agents, are useful in achieving non-antagonistic effects when combinations of drugs are administered.

Abstract: This invention relates to encapsulation of drugs and other agents into liposomes.

Abstract: The invention provides methods and compositions for loading an agent, such as econazole, onto a liposome for parental delivery. The loading of the agent into a liposome comprises combining the agent with a micelle-forming compound to form a micelle including the agent, where the agent is releasable from the micelle-forming compound, and adding the micelle to the liposome, where the micelle combines with the liposome such that the agent is loaded into the liposome to form a loaded liposome. The methods are suitable for the loading of poorly soluble agents onto liposome.

Abstract: The invention relates to the formation of multivalent antibody constructs for testing and therapeutic purposes. In one embodiment the constructs consist of antibodies or antibody fragments conjugated to liposomes. The constructs are employed in a cell-based in vitro assay for comparing the therapeutic activity of antibodies or antibody fragments in multivalent form to the same antibodies or fragments in bivalent, free form. The assay is useful for identifying antibodies having potential in vivo activity. Selected antibodies may then be tested in an animal model of a disease state, such as cancer or an autoimmune disorder. Co-delivery of antibodies and chemotherapeutics may also be investigated. In accordance with the invention, a significant enhancement in the activity of antibodies such as trastuzumab and rituximab was observed when these antibodies were presented in the multivalent liposomal form.

Abstract: The use of the maximum tolerated dose (MTD) of individual drugs to determine appropriate administration ratios of drugs for combination therapy, wherein the ratios of drugs are fixed based on the same percentage of the MTD for each drug. Furthermore, antineoplastic compositions comprising liposomal encapsulated gemcitabine alone or in combination with free or liposomal encapsulated antineoplastic agents, such as idarubicin, irinotecan, etopside, cisplatin, cyclophosphamide, doxorubicin, or vincristine are diclosed.

Abstract: This invention relates to encapsulation of drugs and other agents into liposomes.

Abstract: The invention provides methods and compositions for loading an agent onto a liposome for parenteral delivery. The methods are suitable for the loading of poorly soluble agents onto liposomes.

Abstract: Novel lipid-nucleic acid particulate complexes which are useful for in vitro or in vivo gene transfer are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the lipid-nucleic acid complexes form particles wherein the nucleic acid is serum-stable and is protected from degradation. The particles thus formed have access to extravascular sites and target cell populations and are suitable for the therapeutic delivery of nucleic acids.

Abstract: This invention relates to encapsulation of drugs and other agents into liposomes.

Abstract: Methods to prepare compositions which comprise delivery vehicles having stably associated therewith non-antagonistic combinations of two or more agents. The compositions exhibit non-antagonistic effects when combinations of drugs are administered.

Abstract: Compositions which comprise delivery vehicles having stably associated therewith at least one organic acid derivative of a sterol are useful in achieving enhanced cellular delivery of physiologically relevant sphingolipids when the compositions are administered.

Abstract: Compositions which comprise liposomes having stably associated therewith a camptothecin and a fluoropyrimidine are useful in achieving enhanced therapeutic effects when combinations of these drugs are administered.

Abstract: This invention relates to encapsulation of drugs and other agents into liposomes.

Abstract: Compositions which comprise delivery vehicles having stably associated therewith non-antagonistic combinations of two or more agents, such as antineoplastic agents, are useful in achieving non-antagonistic effects when combinations of drugs are administered.

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: Compositions are provided for delivery of a biologically active agent to a cell, comprising a vehicle having the formula: A-(BC) wherein: A is a lipid-based vehicle; B is a moiety comprising an internalizing peptide; C is a moiety comprising a biologically active agent; (BC) is a complex comprising B and C in which B is conjugated to C; and, A is conjugated to (BC).

Abstract: Compositions which comprise liposomes having stably associated therewith a camptothecin and a fluoropyrimidine are useful in achieving enhanced therapeutic effects when combinations of these drugs are administered.

Abstract: This invention relates to encapsulation of drugs and other agents into liposomes.