Abstract: Mixed micelles containing poly(L-histidine-co-phenylalanine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer are a pH-sensitive drug carrier that release the drug in an acidic microenvironment, but not in the blood. Since the microenvironment of solid tumors is acidic, these mixed micelles are useful for treating cancer, including those cancers exhibiting multidrug resistance. Targeting ligands, such as folate, can also be attached to the mixed micelles for enhancing drug delivery into cells. Methods of treating a warm-blooded animal with such a drug are disclosed.

Abstract: Mixed micelles containing poly(L-histidine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer are a pH-sensitive drug carrier that release the drug in an acidic microenvironment, but not in the blood. Since the microenvironment of solid tumors is acidic, these mixed micelles are useful for treating cancer, including those cancers exhibiting multidrug resistance. Targeting ligands, such as folate, can also be attached to the mixed micelles for enhancing drug delivery into cells. Methods of treating a warm-blooded animal with such a drug are disclosed.

Abstract: A drug delivery vehicle for targeted delivery of a drug mimics viral properties of size, capsid-like protein capsule, cell-specific entry, toxin release, destruction of infected cells, and migration to neighboring cells. This vehicle, termed a virogel, contains a hydrophobic polymeric core, a hydrophilic inner shell, a hydrophilic outer shell, and a ligand. An illustrative drug-loaded virogel includes poly(L-histidine-co-phenylalanine) as the core, doxorubicin loaded in the core, polyethylene glycol as the inner shell, bovine serum albumin as the outer shell, and folic acid as the ligand.

Abstract: Drug delivery compositions for specific delivery of a drug to a tumor are described. These compositions include a core for sequestering the drug and a shell to which a ligand is attached for delivery of a drug to target cells. Since normal cells may also be targeted by the ligand, the compositions embed the ligand in the shell until the localized conditions surrounding the tumor cause the ligand to be displayed on the surface of the shell. One composition exhibits shrinkage of the shell at tumor pH, whereas another composition exhibits extension of the ligand at tumor pH. Still another composition causes the ligand to be exhibited at an elevated temperature.

Abstract: Oligomeric sulfonamides for use as endosomolytic reagents for transfection with polymeric or lipid-based vectors are described. A mixture of an oligomeric sulfonamide with a polymeric or lipid-based gene carrier and a nucleic acid results in a polyplex that exhibits 6-12-fold better gene expression than controls. A method of transfecting cells in vitro is carried out by contacting cultured mammalian cells with an effective amount of a polyplex.

Abstract: Drug delivery compositions for specific delivery of a drug to a tumor are described. These compositions include a core for sequestering the drug and a shell to which a ligand is attached for delivery of a drug to target cells. Since normal cells may also be targeted by the ligand, the compositions embed the ligand in the shell until the localized conditions surrounding the tumor cause the ligand to be displayed on the surface of the shell. One composition exhibits shrinkage of the shell at tumor pH, whereas another composition exhibits extension of the ligand at tumor pH. Still another composition causes the ligand to be exhibited at an elevated temperature.

Abstract: Mixed micelles containing poly(L-histidine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer are a pH-sensitive drug carrier that release the drug in an acidic microenvironment, but not in the blood. Since the microenvironment of solid tumors is acidic, these mixed micelles are useful for treating cancer, including those cancers exhibiting multidrug resistance. Targeting ligands, such as folate, can also be attached to the mixed micelles for enhancing drug delivery into cells. Methods of making poly(L-histidine), synthetic intermediates, and block copolymers are also described.

Abstract: Disclosed are liquefied embolic materials capable of sol-gel phase transition in response to in vivo conditions, including temperature, ionic strength, and pH, and their uses. The liquefied embolic materials are made of copolymers based on temperature-sensitive isopropylacrylamide and ionic strength- and/or pH-sensitive monomers. In addition to finding excellent applications in the embolotherapy, the embolic materials can be used as extracellular matrixes for cell culture and for drug-delivery systems for cancer therapy.

Abstract: A biosensor (10) has a hydrogel (30) in a rigid and referably biocompatible enclosure (20). The hydrogel (30) includes an immobilized glucose-binding molecule such as concanavalin A (Con A) and an immobilized hexose saccharide such as a-D-mannopyranoside. The immobilized hexose saccharide competitively binds with free glucose to the glucose-binding molecules, thus changing the number of crosslinks in the hydrogel (30), which changes hydrogel swelling tendency and the pressure of the hydrogel in its confined space in proportion to the concentration of free glucose. By measuring the change in hydrogel pressure with a pressure transducer (40), the biosensor (10) is able to accurately measure the concentration of the tree glucose molecule without the problem of oxygen limitations and interference encountered by prior art biosensors.

Abstract: A biosensor (10) has a pH-sensitive polymeric hydrogel (30) in a rigid and preferably biocompatible enclosure (20). The hydrogel (30) includes an immobilized oxidoreductase enzyme such as glucose oxidase. The oxidoreductase enzyme catalyzes a chemical reaction consuming an organic molecule and producing a byproduct. The hydrogel (30) changes its osmotic pressure in proportion to the concentration of a byproduct. By measuring the change in osmotic pressure with a pressure transducer (40), the biosensor (10) is able to accurately measure the concentration of the organic molecule without the problem of interference encountered by prior art biosensors. A battery (64) powered telemeter (60) operably engaged to the pressure transducer (40) sends a radio data signal to a receiver (66) operably attached to a computer (62).

Abstract: There are disclosed pH-sensitive polymers containing sulfonamide groups, which can be changed in physical properties, such as swellability and solubility, depending on pH and which can be applied for a drug-delivery system, bio-material, sensor, etc, and a preparation method therefor. The pH-sensitive polymers are prepared by introduction of sulfonamide groups, various in pKa, to hydrophilic groups of polymers either through coupling to the hydrophilic groups, such as acrylamide, N,N-dimethylacrylamide, acrylic acid, N-isopropylacrylamide, etc, of polymers or copolymerization with other polymerizable monomers. These pH-sensitive polymers may have a structure of linear polymer, grafted copolymer, hydrogel or interpenetrating network polymer.

Abstract: A system and method for the parenteral delivery of a drug in a biodegradable polymeric matrix to a warm blooded animal as a liquid with the resultant formation of a gel depot for the controlled release of the drug. The system comprises an injectable biodegradable block copolymeric drug delivery liquid having reverse thermal gelation properties. The delivery liquid is an aqueous solution having dissolved or dispersed therein an effective amount of a drug intimately contained in a biodegradable block copolymer matrix. The copolymer has a reverse gelation temperature below the body temperature of the animal to which it is administered and is made up of (i) a hydrophobic A polymer block comprising a member selected from the group consisting of poly(.alpha.-hydroxy acids) and poly(ethylene carbonates) and (ii) a hydrophilic B polymer block comprising a polyethylene glycol. Prior to use the liquid is maintained at a temperature below the reverse gelation temperature of the block copolymer.