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 an implantable solid polymer delivery composition that can be formulated to release a bioactive agent to an interior body site at a controlled rate over an extended period of time by adjusting the various components of the composition. The controlled delivery of the composition avoids an initial drug spike, resulting in a smooth delivery profile over time. Polymer layers in the composition can be porous and are both biodegradable in water and body enzymes and biocompatible. Methods of making the implantable solid polymer compositions and methods of delivering a bioactive agent at a controlled rate to an interior body site are also provided.

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, 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 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 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 is based on the discovery that a vascular stent or other implantable medical device can be coated with a biodegradable biocompatible polymer to which is attached a bioligand that specifically captures progenitors of endothelial cells (PECs) from the circulating blood to promote endogenous formation of healthy endothelium in Type II diabetics. In one embodiment, the bioligand is a peptide that specifically binds to an integrin receptor on PECs. The invention also provides methods for using such vascular stents and other implantable devices to promote vascular healing in Type II diabetics, for example following mechanical intervention.

Abstract: The present invention provides wound dressings, optionally surgically implantable, containing biodegradable, polymers and hydrogels having allogenic or autologous precursor cells, such as stem cells and progenitor cells dispersed within. Alternatively, the wound dressings can have conditioned medium obtained from the precursor cells dispersed within. The wound dressings promote tissue restoration processes at a site of application or implantation. Additional bioactive agents can also be dispersed within the polymer/hydrogel matrix, which can be formulated to biodegrade at a controlled rate by adjusting the composition. Methods are also provided for using such biodegradable wound dressings as a delivery device or carrier for the precursor cells, conditioned medium and bioactive agents, or as coatings on implantable medical devices, to promote tissue restoration at a lesion site.

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 metal-chelating poly(ether amide) polymers useful in preparation of polymer compositions for delivering a variety of cargo molecules, such as bioactive agents. In solution metal ions and cargo molecules, such as vaccine epitopes, that include metal avid amino acids can be loaded into the polymer compositions and held in a non-covalent complex. Nanoparticles of such polymer compositions can also be prepared directly from the solution.

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 liposomal particle compositions, which incorporate a lipophilic biodegradable polymer, such as amino acid-containing polyester amide (PEA), polyester urethane (PEUR), and polyester urea (PEU), throughout the particles to stabilize the composition for in vivo delivery in of an incorporated biologic agent. For oral delivery, a biologic, such as insulin, is conjugated directly to the polymer. Lipids in the particle are selected to further stabilize the composition during fabrication and digestion, providing sustained delivery of the biologic with native activity. Methods of making and using the invention compositions to administer the biologic agent in vivo are also included.

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 synthetic vaccines against a variety of pathogenic organisms and tumor cells in humans and other mammals based on biodegradable polymers containing polyester amide (PEA), polyester urethane (PEUR), and polyester urea (PEU) and immunostimulatory adjuvants. The vaccines can be formulated as a liquid dispersion of polymer particles or molecules in which are dispersed an immunostimulatory adjuvant, such as a TLR agonist, and whole protein or peptidic antigens containing MHC class I or class II epitopes derived from organism or tumor cell proteins. Methods of inducing an immune response via intracellular mechanisms to the pathogenic organism or tumor cells specific for the antigen in the invention compositions are also included.

Abstract: The invention provides aliphatic epoxy-containing PEA polymer compositions with film-forming properties. The aliphatic epoxy di-acids used in the invention PEA compositions include non-toxic fatty aliphatic epoxy homologs. A second, C-protected L-lysine-based monomer can be introduced into the polymer to provide additional chain flexibility. The invention PEA polymer compositions are useful for delivery of bioactive agents when administered internally or used in the manufacture of implantable medical devices. Biodegradable hydrogels can be made using the invention epoxy-containing PEAs.

Abstract: The present invention provides wound dressings, optionally surgically implantable, containing biodegradable, polymers and hydrogels having allogenic or autologous precursor cells, such as stem cells and progenitor cells dispersed within. Alternatively, the wound dressings can have conditioned medium obtained from the precursor cells dispersed within. The wound dressings promote tissue restoration processes at a site of application or implantation. Additional bioactive agents can also be dispersed within the polymer/hydrogel matrix, which can be formulated to biodegrade at a controlled rate by adjusting the composition. Methods are also provided for using such biodegradable wound dressings as a delivery device or carrier for the precursor cells, conditioned medium and bioactive agents, or as coatings on implantable medical devices, to promote tissue restoration at a lesion site.

Abstract: The present invention provides adhesion barrier compositions based on a solution of at least one of a biodegradable polyester amide (PEA), polyester urethane (PEUR), or polyester urea (PEU) polymers, dissolved in a biocompatible solvent. The compositions can be applied to a tissue surface, such as in open surgery, as a viscous liquid which forms an adhesive film upon being sprayed or painted onto the tissue surface. Alternatively, the composition can be applied to the tissue surface as a preformed solid layer or double layer (either porous or non-porous) that adheres to the tissue surface.