Abstract: The present invention provides compositions and devices that release (a) a nitric oxide (NO) donor and/or NO, and (b) an agent that aggregates and/or trimerizes the Fas receptor, such as but not limited to a Fas-ligand (FasL). In certain embodiments, the invention includes a stent that elutes (a) a NO donor and/or NO, and (b) FasL. In other embodiments, the invention includes methods of treating a condition, such as intimal hyperplasia, in a subject by administering a stent that releases (a) a NO donor and/or NO, and (b) FasL.

Abstract: Brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery (CED) have been developed. In the preferred embodiment, these are loaded with FDA-approved compounds, identified through library screening to target brain cancer stem cells (BSCSs). The particles are formed by emulsifying a polymer-drug solution, then removing solvent and centrifuging at a first force to remove the larger particles, then collecting the smaller particles using a second higher force to sediment the smaller particles having a diameter of less than 100 nm, more preferably less than 90 nanometers average diameter, able to penetrate brain interstitial spaces.

Abstract: Modular nanoparticle vaccine compositions and methods of making and using the same have been developed. Modular nanoparticle vaccine compositions comprise an antigen encapsulated in a polymeric particle and adaptor elements which modularly couple functional elements to the particle. The modular design of these vaccine compositions, which involves flexible addition and subtraction of antigen, adjuvant, immune potentiators, molecular recognition and transport mediation elements, as well as intracellular uptake mediators, allows for exquisite control over variables that are important in optimizing an effective vaccine delivery system.

Abstract: Modular nanoparticle vaccine compositions and methods of making and using the same have been developed. Modular nanoparticle vaccine compositions comprise an antigen encapsulated in a polymeric particle and adaptor elements which modularly couple functional elements to the particle. The modular design of these vaccine compositions, which involves flexible addition and subtraction of antigen, adjuvant, immune potentiators, molecular recognition and transport mediation elements, as well as intracellular uptake mediators, allows for exquisite control over variables that are important in optimizing an effective vaccine delivery system.

Abstract: Modular nanoparticle vaccine compositions and methods of making and using the same have been developed. Modular nanoparticle vaccine compositions comprise an antigen encapsulated in a polymeric particle and adaptor elements which modularly couple functional elements to the particle. The modular design of these vaccine compositions, which involves flexible addition and subtraction of antigen, adjuvant, immune potentiators, molecular recognition and transport mediation elements, as well as intracellular uptake mediators, allows for exquisite control over variables that are important in optimizing an effective vaccine delivery system.

Abstract: Brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery (CED) have been developed. In the preferred embodiment, these are loaded with FDA-approved compounds, identified through library screening to target brain cancer stem cells (BSCSs). The particles are formed by emulsifying a polymer-drug solution, then removing solvent and centrifuging at a first force to remove the larger particles, then collecting the smaller particles using a second higher force to sediment the smaller particles having a diameter of less than 100 nm, more preferably less than 90 nanometers average diameter, able to penetrate brain interstitial spaces.

Abstract: Modular nanoparticle vaccine compositions and methods of making and using the same have been developed. Modular nanoparticle vaccine compositions comprise an antigen encapsulated in a polymeric particle and adaptor elements which modularly couple functional elements to the particle. The modular design of these vaccine compositions, which involves flexible addition and subtraction of antigen, adjuvant, immune potentiators, molecular recognition and transport mediation elements, as well as intracellular uptake mediators, allows for exquisite control over variables that are important in optimizing an effective vaccine delivery system.

Abstract: Polymeric microparticles are used to deliver recombinagenic or mutagenic nucleic acid molecules such as donor nucleic acid alone, or in combination with triplex-forming molecules, to induce a site-specific mutation in the target DNA. Target cells endocytose the particles, releasing the nucleic acid molecules inside of the cell, where they induce mutagenesis or recombination at a target site. The examples demonstrate that triplex forming oligonucleotides, preferably PNAs, preferably in combination with a donor nucleotide molecule, can be encapsulated into polymeric microparticles, which are delivered into cells. Results demonstrate significantly greatly levels of uptake and expression, and less cytotoxicity, as compared to direct transfer of the nucleic acid molecules into the cell by nucleofection.

Abstract: Methods for ex vivo administration of drugs to grafts using polymeric micro- and nanoparticles and applications for these methods are described herein. The particles contain encapsulated molecules which are released locally at the site of implantation and function to prevent graft rejection or aid in the proper adaptation of the graft to the host. The disclosed methods may be used to inhibit or reduce hyperplasia and stenosis of vascular grafts or to prevent graft rejection.

Abstract: Modular nanoparticle vaccine compositions and methods of making and using the same have been developed. Modular nanoparticle vaccine compositions comprise an antigen encapsulated in a polymeric particle and adaptor elements which modularly couple functional elements to the particle. The modular design of these vaccine compositions, which involves flexible addition and subtraction of antigen, adjuvant, immune potentiators, molecular recognition and transport mediation elements, as well as intracellular uptake mediators, allows for exquisite control over variables that are important in optimizing an effective vaccine delivery system.

Abstract: Polymeric delivery devices have been developed which combine high loading/high density of molecules to be delivered with the option of targeting. As used herein, “high density” refers to microparticles having a high density of ligands or coupling agents, which is in the range of 1000-10,000,000, more preferably between 10,000 and 1,000,000 ligands per square micron of microparticle surface area. A general method for incorporating molecules into the surface of biocompatible polymers using materials with an HLB of less than 10, more preferably less than 5, such as fatty acids, has been developed. Because of its ease, generality and flexibility, this method has widespread utility in modifying the surface of polymeric materials for applications in drug delivery and tissue engineering, as well other fields.

Abstract: Polymeric microparticles have been developed which encapsulate therapeutic compounds such as drugs, cellular materials or components, and antigens, and can have targeting ligands directly bound to the microparticle surface. Preferred applications include use in tissue engineering matrices, wound dressings, bone repair or regeneration materials, and other applications where the microparticles are retained at the site of application or implantation. Another preferred application is in the use of microparticles to deliver anti-proliferative agents to the lining of blood vessels following angioplasty, transplantation or bypass surgery to prevent or decrease restenosis, and in cancer therapy. In still another application, the microparticles are used to treat or prevent macular degeneration when administered to the eye, where agents such as complement inhibitors are administered.

Abstract: Polymeric microparticles have been developed which encapsulate therapeutic compounds such as drugs, cellular materials or components, and antigens, and can have targeting ligands directly bound to the microparticle surface. Preferred applications include use in tissue engineering matrices, wound dressings, hone repair or regeneration materials, and other applications where the microparticles are retained at the site of application or implantation. Another preferred application is in the use of microparticles to deliver anti-proliferative agents to the lining of blood vessels following angioplasty, transplantation or bypass surgery to prevent or decrease restenosis, and in cancer therapy. In still another application, the microparticles are used to treat or prevent macular degeneration when administered to the eye, where agents such as complement inhibitors are administered.

Abstract: Polymeric microparticles have been developed which encapsulate therapeutic compounds such as drugs, cellular materials or components, and antigens, and can have targeting ligands directly bound to the microparticle surface. Preferred applications include use in tissue engineering matrices, wound dressings, bone repair or regeneration materials, and other applications where the microparticles are retained at the site of application or implantation. Another preferred application is in the use of microparticles to deliver anti-proliferative agents to the lining of blood vessels following angioplasty, transplantation or bypass surgery to prevent or decrease restenosis, and in cancer therapy. In still another application, the microparticles are used to treat or prevent macular degeneration when administered to the eye, where agents such as complement inhibitors are administered.

Abstract: Polymeric delivery devices have been developed which combine high loading/high density of molecules to be delivered with the option of targeting. As used herein, “high density” refers to microparticles having a high density of ligands or coupling agents, which is in the range of 1000-10,000,000, more preferably between 10,000 and 1,000,000 ligands per square micron of microparticle surface area. A general method for incorporating molecules into the surface of biocompatible polymers using materials with an HLB of less than 10, more preferably less than 5, such as fatty acids, has been developed. Because of its ease, generality and flexibility, this method has widespread utility in modifying the surface of polymeric materials for applications in drug delivery and tissue engineering, as well other other fields.

Abstract: One aspect of the present invention relates to a nucleic acid delivery system including a polymeric structure formed of a biocompatible polymer and a mixture comprising one or more nucleic acid molecules and a first co-dispersant, the mixture being contained within the polymeric structure, wherein the first co-dispersant is present in an amount effective to control diffusion of the one or more nucleic acid from the polymeric structure. Compositions including the nucleic acid delivery system and a pharmaceutically-acceptable carrier are disclosed. Methods of making the nucleic acid delivery system and their use in delivering nucleic acid into a patient and modifying gene expression in a target cell are also disclosed.

Abstract: A genus specific chlamydia oral or injectable vaccine is provided which comprises an anti-idiotype antibody capable of producing in an animal an anti-idiotypic antibody or Fab fragment thereof enclosed in microspheres formed of a pharmacologically acceptable polymer is capable of producing in an animal an anti-anti-idiotypic immune response (serum antibody, secretory antibody or T-cell responsee) which recognizes a glycolipid exoantigen (GLXA) of chlamydia. The oral or injectable vaccine is produced from an idiotypic antibody to GLXA which, in turn, is utilized to produce the anti-idiotypic antibody.