Abstract: Compositions containing particles of biologically active agents with sizes in the micron and submicron range and methods for making and using such particles are described herein. In the preferred embodiment the biologically active agents are peptides, proteins, nucleic acid molecules, or hydrophilic synthetic molecules. The particles have a size ranging from an average diameter of about 100 nm to about 2000 nm, preferably about 200 nm to 600 nm. Optionally the biologically active agents contain a polymeric coating. The particles are formed by adding a biologically active agent to an aqueous solution, mixing a nonsolvent that is miscible with water with the aqueous solution, and precipitating particles of the biologically active agents out of the nonsolvent: aqueous solution combination. The nonsolvent is typically a C1 to C6 alcohol, preferably a C2 to a C5 alcohol. In the preferred embodiment, the nonsolvent is tert-butyl alcohol.

Abstract: The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.

Abstract: Bioadhesive macrosphere delivery systems (“BDDS”) having prolonged gastric retention time due to bioadhesion rather than physical density or size are described. In general, the macrospheres have diameters that are greater than 200 microns, more preferably greater than 500 microns. The bioadhesive macrospheres are released in the stomach where they reside in close proximity to the gastric mucosa for a prolonged period of time. Increased residence of BDDS in the upper GI can lead to increased systemic absorption of drug in the preferred site of systemic absorption, namely the upper GI tract (upper to mid-jejunum). The BDDS may be engineered either as a capsule with drug delivery controlled by a diffusion-limited membrane or degradable shell, or as a solid matrix system with drug delivery controlled by a combination of diffusion and polymer degradation kinetics.

Abstract: The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.

Abstract: Bioactive agents may be reproducibly converted into particles having diameters in the range of about 5 to about 2000 nanometers (nm). Conversion is accomplished by dissolving the bioactive agent in a solvent for the bioactive agent, and rapidly altering the polarity of the solution to make it a non-solvent for the bioactive agent, for example by diluting the bioactive agent solution with an excess of a liquid that is a non-solvent for the bioactive agent but is miscible with the solvent. Precipitated bioactive agent nanoparticles are collected by centrifugation, filtration or lyophilization. The nanoparticles have a relatively narrow size distribution, and the average diameter can be controlled by choice of solvent and non-solvent. The nanoparticles are typically amorphous. A surfactant may be added to ensure dispersion of the particles when administered. In the preferred embodiment, the bioactive agent is a drug with low aqueous solubility.

Abstract: The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.

Abstract: A means for obtaining efficient introduction of exogenous genes into a patient, with long term expression of the gene, is disclosed. The gene, under control of an appropriate promoter for expression in a particular cell type, is encapsulated or dispersed with a biocompatible, preferably biodegradable polymeric matrix, where the gene is able to diffuse out of the matrix over an extended period of time, for example, a period of three to twelve months or longer. The matrix is preferably in the form of a microparticle such as a microsphere (where the gene is dispersed throughout a solid polymeric matrix) or microcapsule (gene is stored in the core of a polymeric shell), a film, an implant, or a coating on a device such as a stent. The size and composition of the polymeric device is selected to result in favorable release kinetics in tissue.

Abstract: The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.

Abstract: A process for preparing nanoparticles and microparticles is provided. The process involves forming a mixture of a polymer and a solvent, wherein the solvent is present in a continuous phase and introducing the mixture into an effective amount of a nonsolvent to cause the spontaneous formation of microparticles.

Abstract: Methods for inducing a thermoplastic polymer, which can be non-mesogenic, to exhibit liquid crystalline properties have been developed. The method includes the steps of (a) heating the polymer from an initial temperature below its glass transition temperature (Tg) to a temperature greater than its Tg and below its melting temperature (Tm); (b) exposing the polymer to a pressure greater than about 2 metric tons/in2, preferably between about 2 and 10 metric tons/in2, preferably for at least about one minute, while maintaining the temperature greater than its Tg; and (c) cooling the polymer below the Tg while maintaining the elevated pressure. Unlike many prior art transition processes which are reversible, this process provides a liquid crystal state that can be maintained for years at ambient conditions. In a preferred embodiment, the plastics are bioerodible thermoplastic polymers, such as polyanhydrides, some polyesters, polyamides, and polyaromatics.

Abstract: The invention involves methods and products for oral gene therapy. Genes under the control of promoters are protectively contained in microparticles and delivered to cells in operative form, thereby obtaining noninvasive gene delivery for gene therapy.

Abstract: Methods for inducing a thermoplastic polymer, which can be non-mesogenic, to exhibit liquid crystalline properties have been developed. The method includes the steps of (a) heating the polymer from an initial temperature below its glass transition temperature (Tg) to a temperature greater than its Tg and below its melting temperature (Tm); (b) exposing the polymer to a pressure greater than about 2 metric tons/in2, preferably between about 2 and 10 metric tons/in2, preferably for at least about one minute, while maintaining the temperature greater than its Tg; and (c) cooling the polymer below the Tg while maintaining the elevated pressure. Unlike many prior art transition processes which are reversible, this process provides a liquid crystal state that can be maintained for years at ambient conditions. In a preferred embodiment, the plastics are bioerodible thermoplastic polymers, such as polyanhydrides, some polyesters, polyamides, and polyaromatics.

Abstract: A means for obtaining efficient introduction of exogenous genes into a patient, with long term expression of the gene, is disclosed. The gene, under control of an appropriate promoter for expression in a particular cell type, is encapsulated or dispersed with a biocompatible, preferably biodegradable polymeric matrix, where the gene is able to diffuse out of the matrix over an extended period of time, for example, a period of three to twelve months or longer. The matrix is preferably in the form of a microparticle such as a microsphere (where the gene is dispersed throughout a solid polymeric matrix) or microcapsule (gene is stored in the core of a polymeric shell), a film, an implant, or a coating on a device such as a stent. The size and composition of the polymeric device is selected to result in favorable release kinetics in tissue.

Abstract: A process for preparing nanoparticles and microparticles is provided. The process involves forming a mixture of a polymer and a solvent, wherein the solvent is present in a continuous phase and introducing the mixture into an effective amount of a nonsolvent to cause the spontaneous formation of microparticles.

Abstract: The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.

Abstract: A process is provided for making dry, micronized particles of an agent, such as a drug. The method includes (a) dissolving a macromolecular material, preferably a polymer, in an effective amount of a solvent, to form a solution; (b) dissolving or dispersing the agent in the solution to form a mixture; (c) freezing the mixture; and (d) drying by vacuum the mixture to form solid particles of the agent dispersed in solid macromolecular material. The micronization in this process occurs directly in a macromolecular matrix and hardening of the particles of agent by solvent removal takes place by lyophilization of the bulk matrix, which stabilizes the drug particles during hardening and prevents coalesence, thereby resulting in smaller final drug particles. The method is particularly preferred for protein agents. The process can be used in conjunction with a standard microencapsulation technique, typically following separation of the agent from the macromolecular matrix.

Abstract: A process is provided for making dry, micronized particles of an agent, such as a drug. The method includes (a) dissolving a macromolecular material, preferably a polymer, in an effective amount of a solvent, to form a solution; (b) dissolving or dispersing the agent in the solution to form a mixture; (c) freezing the mixture; and (d) drying by vacuum the mixture to form solid particles of the agent dispersed in solid macromolecular material. The micronization in this process occurs directly in a macromolecular matrix and hardening of the particles of agent by solvent removal takes place by lyophilization of the bulk matrix, which stabilizes the drug particles during hardening and prevents coalesence, thereby resulting in smaller final drug particles. The method is particularly preferred for protein agents. The process can be used in conjunction with a standard microencapsulation technique, typically following separation of the agent from the macromolecular matrix.

Abstract: Methods and compositions are provided for enhancing the bioadhesive properties of polymers used in drug delivery systems. The bioadhesive properties of a base polymer are enhanced by incorporating a short chain polymer with one or more free carboxylic groups into the base polymer to enhance the ability of the base polymer to adhere to a tissue surface such as a mucosal membrane. The short chain polymers can be incorporated within a wide range of base polymers including proteins, polysaccharides and synthetic biocompatible polymers. In one embodiment, short chain polymers can be incorporated within base polymers used to form or coat drug delivery systems, such as microspheres, which contain a drug or diagnostic agent. The short chain polymers can either be solubilized and blended with the base polymer before manufacture or else used as a coating with base polymers over existing systems.

Abstract: Sustained delivery compositions which modulate the release of incorporated prophylactic, therapeutic, and/or diagnostic agents, and methods of preparation and use thereof, are disclosed. The compositions include a biocompatible polymeric matrix; a prophylactic, therapeutic, and/or diagnostic agent dispersed within the polymeric matrix; and a monovalent cation component which is separately dispersed within the polymeric matrix. The monovalent cation component modulates the release of the incorporated agent from the polymeric matrix. The compositions can be prepared by dissolving a biocompatible polymer in a solvent to form a polymer solution, and separately dispersing a monovalent cation and a prophylactic, therapeutic, and/or diagnostic agent within the polymer solution. The polymer solution is then solidified to form a polymeric matrix, wherein a significant amount of the monovalent cations is dispersed in the polymeric matrix separately from the incorporated agent.

Abstract: Two or more hydrophilic polymers that are not soluble in each other at a particular concentration and temperature, but which have a positive spreading coefficient in solution, are used to form multi-layered polymeric microspheres. The multi-layer microspheres produced by the method are distinguished by extremely uniform dimensioned polymer layers and actual incorporation of a substance to be delivered into the polymer layers. In the preferred embodiment of the method, two polymers are dissolved in an aqueous solvent, the substance to be incorporated is dispersed or dissolved in the polymer solution, the mixture is suspended in an organic solvent or polymer/water mixture and stirred, and the solvent is slowly evaporated, creating microspheres with an inner core formed by one polymer and an outer layer formed by the second polymer.