Abstract: Formulations for controlled, prolonged release of bioactive molecules such as therapeutic proteins, peptides and oligonucleotides have been developed. These formulations are based on solid microparticles or nanoparticles formed of the combination of biodegradable, synthetic polymers such as poly (lactic acid) (PLA), poly (glycolic acid) (PGA), and copolymers thereof. Bioactive molecules are coupled to hydrophilic polymers such as polyethylene glycol or polypropylene glycol and formulated to provide controlled release. The bioactive molecules are more stable, less immunogenic and have improved release rate profiles with lower burst levels and increased drug loading relative to the same bioactive molecules lacking coupled hydrophilic polymers. The controlled release formulations can be administered by injection, by inhalation, nasally, or orally.

Abstract: The present invention provides sustained release formulations of estradiol metabolites whereby the in vivo pharmacokinetics are manipulated by a method selected from the group consisting of chemical modification, crystal packing formation, particle size or a combination thereof. Such compositions are useful in the long-term treatment of a wide variety of diseases.

Abstract: The apparatus, methods and compositions of the present invention are of use for the production of emulsion-based microparticles containing a biological or chemical agent. The apparatus and methods of the present invention provide for a low-shear, non-turbulent, production of emulsion-based microparticles that provides a narrow, reproducible, particle size distribution, capable of use with both large and small volumes that is conveniently scaled up while providing predictable emulsion properties. The methods include production of emulsion-based microparticles containing a biological or chemical agent which, when suspended in a diluent, are syringable through a needle without clumping of the microparticles or clogging of the needle.

Abstract: The compositions disclosed herein are for use as controlled release therapeutics for the treatment of a wide variety of diseases. In particular, the compositions provide water soluble bioactive agents, organic ions and polymers where the bioactive agent is efficiently released over time with minimal degradation products. The resulting controlled release composition is capable of administration in a decreased dose volume due to the high drug content and predominance of non-degraded bioactive agent after release. Additionally, the compositions, of the present invention are capable of long term, sustained releases.

Abstract: The invention is directed to a single-step method for rapidly and efficiently preparing protein-polymer conjugates, including an insulin-polymer conjugate. According to the method of the present invention, a protein and hydrophilic polymer are contacted in the presence of at least one organic solvent and at least one metal chelator, under conditions that promote the formation of a conjugate of the protein and polymer. Thus, the invention is directed to the site-specific modification of selected proteins, such as insulin, with poly(ethylene glycol) at residue PheB 1. The invention also provides a pharmaceutical formulation for encapsulating the conjugate in a biodegradable polymer.

Abstract: A method and composition for the encapsulation of hydrophilic molecules in submicron particles is disclosed. The particles are composed of a water-in-oil microemulsion surrounded by one or more biocompatible polymers.

Abstract: Formulations for controlled, prolonged release of bioactive molecules such as therapeutic proteins, peptides and oligonucleotides have been developed. These formulations are based on solid microparticles or nanoparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof. Bioactive molecules are coupled to hydrophilic polymers such as polyethylene glycol or polypropylene glycol and formulated to provide controlled release. The bioactive molecules are more stable, less immunogenic and have improved release rate profiles with lower burst levels and increased drug loading relative to the same bioactive molecules lacking coupled hydrophilic polymers. The controlled release formulations can be administered by injection, by inhalation, nasally, or orally.