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 present invention is directed to a multilayered dosage form which is adapted for retention in the stomach and useful for the prolonged delivery of an active agent to a fluid environment of use. The active agent dosage form is a multilayer core, often bilayer, formed of polymer matrices that swell upon contact with the fluids of the stomach. At least one layer of the multilayered dosage form includes an active agent. A portion of the polymer matrices are surrounded by a band of insoluble material that prevents the covered portion of the polymer matrices from swelling and provides a segment of the dosage form that is of sufficient rigidity to withstand the contractions of the stomach and delay expulsion of the dosage form from the stomach until substantially all of the active agent has been dispensed.

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: 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: An osmotic caplet is disclosed comprising an osmotic caplet exit for delivering a preselected dose of drug to a patient in need of therapy.

Abstract: This invention relates to stable non-aqueous formulations which are suspensions of proteinaceous substances or nucleic acids in non-aqueous, anhydrous, aprotic, hydrophobic, non-polar vehicles with low reactivity. More specifically, the present invention relates to stable protein or nucleic acid formulations wherein the compound remains in stable, dry powder form, yet the formulation is flowable and, therefore amenable to delivery to an animal via injection transdermal administration, oral delivery or using an implantable device for sustained delivery. These stable formulations may be stored at elevated temperatures (e.g., 37° C.) for long periods of time and are especially useful as flowable formulations which can be shipped and/or stored at high temperatures or in implantable delivery devices for long term delivery (e.g., 1-12 months or longer) of drug.

Abstract: A dosage form is disclosed comprising means for delaying the delivery of drug from the dosage form following the administration of the dosage form to a patient in need of drug therapy.

Abstract: A minimally invasive transdermal nucleic acid sampling method comprises piercing through the outermost layer of the skin and into the underlying epidermis with a plurality of microprojections. Living skin cells in the underlying epidermis are disrupted, causing them to release their contents including their nucleic acids (i.e., DNA, RNA, fragments thereof or other polynucleic acid material found in the nucleii and/or mitochondria of cells). The nucleic acid is collected on the surfaces of the microprojections and/or in a separate nucleic acid collection reservoir. The collected nucleic acid is then analyzed using standard polymerase chain reaction (PCR) techniques. Optionally a suction device applies a partial vacuum through openings in the microprojection member to the microcuts in the skin for enhanced efflux of intracellular and extracellular (i.e., body) fluids containing the nucleic acid.

Abstract: An apparatus for the electrically assisted delivery of therapeutic agent is described. An apparatus of the invention has rigid zones or regions which are physically connected by flexible means such as a web. The flexible means permits the rigid zones to move independently with respect to each other while remaining physically connected or coupled. In a preferred embodiment, the rigid zones are physically and electronically coupled by the flexible means. In another preferred embodiment, the skin side of the rigid zones has a radius of curvature which approximates that of the body site to which the device is to be attached. A method of increasing the body or surface conformability of a rigid electrotransport device is described. The method involves the step of intentionally placing rigid subcomponents of the device in physically separate zones within the device. The rigid zones are separate and are coupled by flexible connector means.

Abstract: An electrotransport device and method of operating same provides a pulsed DC current of specified frequency and duration which transforms the skin into a higher electrotransport delivery efficiency state.

Abstract: Composition of matter for application to a body surface or membrane to administer fenoldopam by permeation through the body surface or membrane, the composition comprising fenoldopam to be administered, at a therapeutically effective rate, in combination with a permeation enhancer or mixture. Also disclosed are drug delivery devices and methods for the transdermal administration of fenoldopam for the treatment of hypertension, congestive heart failure, and chronic and acute renal failure.

Abstract: An osmotic delivery system for controlled delivery of a beneficial agent includes an implant capsule having a beneficial agent reservoir, an osmotic agent which expands on contact with fluid imbibed through a permeable membrane retained by the implant capsule, a delivery port, and a valve for opening and closing the delivery port. When the osmotic agent expands, a pressure is exerted against a separating member positioned between the beneficial agent reservoir and the osmotic agent. The separating member moves within the capsule, thereby forcing the valve to move a distance such that the beneficial agent can exit the reservoir through the delivery port.

Abstract: Methods and compositions for systemically or locally administering by implantation a beneficial agent to a subject are described, and include, for example, compositions having burst indices of 8 or less for systemic applications and systems releasing 10% or less of the total dose of beneficial agent in the first 24 hours after implantation for local applications. The compositions include a biocompatible polymer, a biocompatible solvent having low water miscibility that forms a viscous gel with the polymer and limits water uptake by the implant, and a beneficial agent.

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: This invention relates to the field of transdermal drug delivery devices and more particularly to improved storage stability thereof. The invention comprises providing a transdermal drug delivery device with a non-occlusive backing or release liner in combination with a degradation protectant such as a desiccant or oxygen scavenger within the sealed pouch containing the device. The combination of the present invention provides increased shelf-life of these devices.

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: The present invention is directed to an active agent dosage form which is adapted for retention in the stomach and useful for the prolonged delivery of a liquid, active agent formulation to a fluid environment of use. The liquid, active agent formulation is sorbed into porous particles that are dispersed in a polymer matrix that swells upon contact with the fluids of the stomach. A portion of the polymer matrix may be surrounded by a band of insoluble material that prevents the covered portion of the polymer matrix from swelling and provides a segment of the dosage form that is of sufficient rigidity to withstand the contractions of the stomach and delay expulsion of the dosage form from the stomach until substantially all of the active agent has been dispensed.

Abstract: The invention is directed to a device for delivering an active agent formulation for a predetermined administration period. An impermeable reservoir is divided into a water-swellable agent chamber and an active agent formulation chamber. Fluid from the environment is imbibed through a semipermeable plug into the water-swellable agent chamber and the active agent formulation is released through a back-diffusion regulating outlet. Delivery periods of up to 2 years are achieved.

Abstract: Dosage forms and methods for providing sustained release of reboxetine are provided. The sustained release dosage forms provide therapeutically effective average steady-state plasma reboxetine concentrations when administered once per day. This once-a-day dosing regimen results in only one peak plasma reboxetine concentration occurrence in each 24 hour period. In addition, the peak plasma reboxetine concentration occurs at a later time following dose administration and exhibits a lesser magnitude than the peak plasma reboxetine concentration that occurs following administration of reboxetine in an immediate-release dosage form.