Abstract: The present invention provides biodegradable polymer particle delivery compositions based on polymers, such as polyester amide (PEA) and polyester urethane (PEUR) polymers, that contain amino acids in the polymer. The polymer particle delivery compositions can be formulated as a liquid dispersion of polymer particles with the bioactive agents dispersed in the particle or conjugated attached to polymer molecules or particle surfaces. The bioactive agents can include drugs, polypeptides, DNA and cells for cell-based therapies using particles sized for local, mucosal or circulatory delivery. Methods of treating a disease by administering to a subject the polymer particle delivery composition, which incorporates a bioactive agent suitable for treatment of the disease, or its symptoms, are also included.

Abstract: The present invention provides biodegradable, biocompatible bis-(?-amino acyl)-diol-diester-containing poly(ester amide) (PEA) and poly(ester urethane) (PEUR) co-polymer compositions with mechanical properties that can be readily tailored by selection of various combinations and proportions of the building blocks of the co-polymers. The compositions are suitable for use in production of drug-releasing biodegradable particles and implantable surgical devices, such as stents and internal fixation devices. The co-polymer compositions, particles and surgical devices biodegrade in vivo by enzymatic action to release bioactive agents in a controlled manner over time as well as biocompatible breakdown products, including one to multiple different amino acids.

Abstract: The invention provides high molecular weight, crystalline or semi crystalline biodegradable and biocompatible poly(ester urea) (PEU) polymers useful for making vascular stents and hard tissue replacement implants, such as bone substitutes. The PEU polymers are based on ? amino acids and are made by a polycondensation reaction. PEU polymer compositions can contain a therapeutic diol incorporated into the polymer backbone that is released from such an implant in situ. Bioactive agents, such as analgesics, antibiotics, and the like, can also be covalently attached to certain PEU polymers for release into tissue surrounding an implant during biodegradation of the polymer.

Abstract: The invention provides new aliphatic diester-di-acid-containing PEA polymer compositions with significant improvement in hydrolytic degradation rates as compared to aliphatic di-acid-containing PEA polymers. The di-acids used in the invention PEA compositions include non-toxic fatty aliphatic homologs. These molecules inherently contain two-ester groups, which easily can be cleaved by biotic (enzymatic) and abiotic hydrolysis. Additional di-acid-type compounds useful for active polycondensation are ?,?-alkylene dicarboxylates composed of short aliphatic non toxic diols and di-acids. In addition, the invention PEA polymer compositions optionally can include a second monomer, such as a C-protected L-lysine-based monomer, to introduce additional chain flexibility into the polymer. The invention PEA polymer compositions are useful for delivery of bioactive agents when administered internally.

Abstract: The present invention provides biodegradable, biocompatible bis-(?-amino acyl)-diol-diester-containing poly(ester amide) (PEA) and poly(ester urethane) (PEUR) co-polymer compositions with mechanical properties that can be readily tailored by selection of various combinations and proportions of the building blocks of the co-polymers. The compositions are suitable for use in production of drug-releasing biodegradable particles and implantable surgical devices, such as stents and internal fixation devices. The co-polymer compositions, particles and surgical devices biodegrade in vivo by enzymatic action to release bioactive agents in a controlled manner over time as well as biocompatible breakdown products, including one to multiple different amino acids.

Abstract: The present invention provides biodegradable polymer particle delivery compositions based on polymers, such as polyester amide (PEA) and polyester urethane (PEUR) polymers, that contain amino acids in the polymer. The polymer particle delivery compositions can be formulated as a liquid dispersion of polymer particles with the bioactive agents dispersed in the particle or conjugated attached to polymer molecules or particle surfaces. The bioactive agents can include drugs, polypeptides, DNA and cells for cell-based therapies using particles sized for local, mucosal or circulatory delivery. Methods of treating a disease by administering to a subject the polymer particle delivery composition, which incorporates a bioactive agent suitable for treatment of the disease, or its symptoms, are also included.

Abstract: The invention provides sequential poly(ester amide)s derived from Proline and that are synthesized by a two-step method, involving a final thermal polyesterification reaction. Molecular weights of polymers prepared by this method are from 14,000 Da to about 77,000 Da.1 When invention proline-based PEAs were thermally characterized, their glass transition temperatures were lower than other alpha-amino acid based poly(ester amides) due to lack of internal hydrogen bonding. These Proline-based PEAs assemble as nano-particles in aqueous solutions and form complexes with various cations and biologies, including hydrophobic small molecule drugs and biologies. Therefore the invention Proline-based PEAs are useful for drug delivery applications requiring a polymer with a molecular weight in the range from 14,000 Da to about 77,000 Da and for fabrication of nanoparticles for delivery of hydrophobic drugs.

Abstract: The invention provides biodegradable PEAs, PEURs and PEUs that are synthesized by solution polycondensation to include ?-amino acids and oligo-ethylene ether segments in the polymer backbone. The polymers can be obtained by substituting oligo-ethylene glycol (OEG) for aliphatic di-acid and diols during their fabrication. Also provided are compositions in which bioactive agents are dispersed in the polymers. The compositions biodegrade by enzymatic action to release incorporated bioactive agents and oligo-ethylene glycol segments, which are fully biodegradable at a molecular weight less than 400 Da. Due to their comparatively rapid surface enzymatic hydrolysis, the compositions can be used to deliver bioactive agents in a controlled manner within a relatively rapid delivery time, such as about 18 to 24 hours.

Abstract: The invention provides AABB-poly(depsipeptide)s (AABB-PDPs), a class of biodegradable polymers composed of ?-amino and ?-hydroxy acids with material properties suitable for biomedical applications. These AABB-PDPs belong to the family of amino acid-based poly(ester amide)s (PEAs), which are characterized by the presence of alternating ester and amide functionalities. Containing four ether groups per basic unit, these polymers degrade rapidly by biotic or abiotic hydrolytic action to release dispersed bioactive agents at a controlled delivery rate, are non-toxic, produce digestible breakdown products, and are easy to fabricate by solution polycondensation.

Abstract: The invention provides elastomeric polymer networks and semi-interpenetrating networks in which a linear PEA, PEUR or PEU polymer is crosslinked by ester or alpha-amino-acid containing cross-linkers that polymerize upon exposure to active species. Bioabsorbable elastomeric internal fixation devices fabricated using such polymer networks and semi-interpenetrating networks are useful for in vivo implant and delivery of a variety of different types of molecules in a time release fashion. Alpha-amino-acid containing ester amide cross-linkers are also provided by the invention.

Abstract: The invention provides elastomeric polymer networks and semi-interpenetrating networks in which a linear PEA, PEUR or PEU polymer is crosslinked by ester or alpha-amino-acid containing cross-linkers that polymerize upon exposure to active species. Bioabsorbable elastomeric internal fixation devices fabricated using such polymer networks and semi-interpenetrating networks are useful for in vivo implant and delivery of a variety of different types of molecules in a time release fashion. Alpha-amino-acid containing ester amide cross-linkers are also provided by the invention.

Abstract: The invention provides gene transfer compositions using as the gene carrier a biodegradable polymer that contains one or more cationic alpha amino acids, such as arginine or agmatine. The compositions form a tight soluble complex with a poly nucleic acid suitable for transfecting target cells to effect translation of the cargo poly nucleic acid by the target cell. Thus, such compounds are useful both in vitro and in vivo.

Abstract: The invention provides biodegradable, cationic compositions based on cationic ?-amino acid-containing PEA, PEUR and PEU polymers for use in preparation of non-viral gene transfer compositions. In the invention gene transfer compositions a poly nucleic acid is condensed with the polymer to form a soluble unit wherein the electrical charge of the poly nucleic acid is neutralized by the polymers. The invention gene transfer compositions can be used to transfect target cells by contact with the target cells.

Abstract: The invention provides bioabsorbable elastomeric arterial support devices fabricated using elastomeric polymer networks and semi-interpenetrating networks in which a linear polymer is crosslinked by ester or alpha-amino-acid containing cross-linkers that polymerize upon exposure to active species. The invention devices are designed for implant into curved segments of artery and can be expanded during arterial implant and cross-linked in vivo in the expanded state to restore a clogged artery to extended function. The invention devices are useful for in vivo implant in diseased arteries and for delivery of a variety of therapeutic molecules in a time release fashion to surrounding tissues to reduce or eliminate arterial response to implant of the device.

Abstract: The present invention provides biodegradable, biocompatible bis-(?-amino acyl)-diol-diester-containing poly(ester amide) (PEA) and poly(ester urethane) (PEUR) co-polymer compositions with mechanical properties that can be readily tailored by selection of various combinations and proportions of the building blocks of the co-polymers. The compositions are suitable for use in production of drug-releasing biodegradable particles and implantable surgical devices, such as stents and internal fixation devices. The co-polymer compositions, particles and surgical devices biodegrade in vivo by enzymatic action to release bioactive agents in a controlled manner over time as well as biocompatible breakdown products, including one to multiple different amino acids.