Abstract: Nanoparticles and nanoparticle-releasing vaginal rings for intermediate- to long-term delivery of drugs to the female genital and reproductive tract have been developed. The nanoparticles are loaded with drugs and coated with a sheddable poly(ethylene glycol) (PEG) layer that promotes mucus penetration and then converts to an adhesive form after penetration. This platform technology readily distributes drug through the mucosa and throughout the vaginal tissue, enhances local retention of drugs within the vaginal tissue, thereby providing a sustained delivery of drugs beyond the natural shedding and turnover of vaginal mucous and epithelial cells.

Abstract: Nanoparticles useful for drug delivery are described. In one aspect, the nanoparticles contain poly(amine-co-ester)s or poly(amine-co-amide)s (PACE) modified with poly(ethylene glycol) (PACE-PEG), and can be optionally blended with a second PACE polymer optionally containing endgroup modifications. In another aspect, the nanoparticles contain a core containing a PACE polymer optionally containing endgroup modifications, and a polymeric surfactant non-covalently conjugated to the surface of the nanoparticles. The nanoparticles contain a peptide or protein targeting moiety that is covalently conjugated to the PACE-PEG polymer or to the surfactant on the surface of the nanoparticles via a linkage that contains a succinimide or substituted sulfone moiety, respectively. The nanoparticles provide as a versatile platform for the delivery of nucleic acids, such as mRNA.

Abstract: Biodegradable controlled release agent implants and methods of making and using thereof, are preferably formed of poly(?-pentadecalactone-co-p-dioxanone) [poly(PDL-co-DO)] or poly(ethylene brassylate-co-dioxanone), a family of polyester copolymers that degrade slowly in the presence of water. The material is suitable as the basis of a biodegradable controlled agent release implant that provides sustained release of a therapeutic such as an antiviral, thereby significantly increasing patent compliance and efficacy. Results show long term co-administration of agents having greater than additive efficacy. The implant may be inserted subcutaneously, allowing degradation over a period of up to about 18 or 24 months, eliminating the need for removal by a trained practitioner.

Abstract: Formulations for treating proliferative disorders have been developed. In some forms, the formulations are in the form of an injectable aqueous solution for treating tumors and contain exatecan mesylate, optionally including an immunostimulatory agent or adjuvant such as an immunostimulatory oligonucleotide (CpG), at a pH at which the exatecan is soluble until the pH is raised by contacting normal tissue. In some forms, the formulations contain core-shell particles, containing an exatecan in its free base form, a hydrophobic core, and a shell, coating, or corona containing hyperbranched polyglycerol in which hydroxyl groups of the hyperbranched polyglycerol are converted to aldehydes, to adhere the particles to tissue.

Abstract: Methods to produce branching poly(amine-co-ester) (bPACE) polymers having more than two end groups per single polymer, where the amine content can be controlled by end-group modification, have been developed. The resulting bPACE polymers are particularly well suited for delivery of nucleic acid molecules, showing strong complexation, stability, better transfection and expanded routes of administration. Advantages of bPACE include polyplexes with branched polymer present positive charges, even with large amount of nucleic acid (strong and rigid complexation to limited number of nucleic acid), even in neutral pH (7.4, PBS). Transfection by bPACE performs better than linear PACE at a lower weight ratio, showing high expression in vivo. Advantages of bPACE also include polyplexes with branched polymer present better stability in neutral pH, physiological condition, maintaining transfection abilities.

Abstract: A method to precisely tailor the surface topography of polymeric nanoparticles having bound thereto polyalkylene oxide, based on tuning the architecture of shape-persistent amphiphilic bottlebrush block copolymer (BBCP) building blocks, has been developed. It was demonstrated that nanoparticle formation and surface topography can be controlled by systematically changing structural parameters of BBCP architecture. The surface topography of PEGylated nanoparticles (nanoparticles having PEO or PEG covalently bound thereto) significantly affects their biological performance.

Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

Abstract: Compositions and methods for fetal or in utero delivery of active agents are provided. The compositions are most typically administered intravenously via the vitelline vein, umbilical vein, or directly into the amniotic cavity of a pregnant mother. Fibroblast growth factor is to correct structural defects of neural tissue.

Abstract: A platform technology provides particle and nucleic acid conjugates, and compositions thereof, with enhanced targeting to cells, tissues, organs. The particles and nucleic acids and other deliverables contain a synthetic binding protein such as a polypeptide monobody covalently conjugated to the surface of the particle or the nucleic acid, for linking a targeting agent to the particle's surface or the nucleic acid. The particles and nucleic acids and other deliverables optionally contain an antibody non-covalently conjugated to the binding protein, via an Fc domain of the antibody. The particles can include therapeutic agents, diagnostic agents, prophylactic agents, or a combination thereof, to be delivered to desired cells, tissues, and/or organs. The particles and nucleic acids and other deliverables can be used in a wide array of applications including, but not limited to, ex vivo perfusion of mammalian organs and in vivo disease treatment.

Abstract: Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.

Abstract: A bioadhesive nanoparticle (BNP) for long-lasting local drug delivery to treat cancer was developed. The bioadhesive nanoparticles (BNP) are composed of biodegradable polymer such as poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG), encapsulating a chemotherapeutic such as camptothecin (CPT). Nanoparticles (NPs) of PLA-HPG are non-adhesive NPs (NNPs), which are stealthy in their native state, but conversion of the vicinal diols of HPG to aldehydes confers the ability to form strong covalent bonds with amine-rich surfaces. The formulation is administered in combination with immunostimulatory molecules such as CPG and shows unexpectedly better killing of cancer cells.

Abstract: The present invention provides cationic polymeric nanoparticles, and nanoparticle formulations thereof. The invention also provides methods for preparing cationic polymeric nanoparticles, and methods of treating diseases, reducing tumor growth, and increasing uptake of a therapeutic agent by a tumor cell in a subject in need thereof.

Abstract: A platform technology provides particle and nucleic acid conjugates, and compositions thereof, with enhanced targeting to cells, tissues, organs. The particles and nucleic acids and other deliverables contain a synthetic binding protein such as a polypeptide monobody covalently conjugated to the surface of the particle or the nucleic acid, for linking a targeting agent to the particle's surface or the nucleic acid. The particles and nucleic acids and other deliverables optionally contain an antibody non-covalently conjugated to the binding protein, via an Fc domain of the antibody. The particles can include therapeutic agents, diagnostic agents, prophylactic agents, or a combination thereof, to be delivered to desired cells, tissues, and/or organs. The particles and nucleic acids and other deliverables can be used in a wide array of applications including, but not limited to, ex vivo perfusion of mammalian organs and in vivo disease treatment.

Abstract: Embodiments of the present invention comprises one or more of an article composed of a copolymer, a copolymer made from a process, and a process for the preparation of a copolymer composition by metal free enzyme ring-opening polymerization of a monomer composition comprising i) an ethylene brassylate monomer; ii) a 1-4 dioxan-2-one (DO); iii) lipase B from Candida antarctica (Novozyme® 435) and at an elevated temperature, processing the monomer reactants i) and ii) to a copolymer via ring-opening polymerization under solvent-free conditions and a nitrogen atmosphere in the absence of a metal and the presence of the lipase to produce a random EB-co-DO copolymer.

Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

Abstract: Compositions and methods for fetal or in utero delivery of active agents are provided. The compositions are most typically administered intravenously via the vitelline vein, umbilical vein, or directly into the amniotic cavity of a pregnant mother. Fibroblast growth factor is to correct structural defects of neural tissue.

Abstract: Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.

Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

Abstract: Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.

Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.