Abstract: Provided herein are compounds that are local anesthetics and useful for inducing selective sensory nerve blockade. Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of inducing selective sensory nerve blockade by administering the compounds and/or compositions to a subject.

Abstract: Provided herein are polypeptides that are truncated modified recombinant forms of ADAMTS13, nucleic acid molecules encoding the polypeptides, drug delivery compositions and pharmaceutical compositions comprising the polypeptides, and methods of using the polypeptides and compositions (e.g., in the treatment of thrombotic thrombocytopenic purpura (TTP)).

Abstract: Provided herein are compositions comprising macromolecular photocleavable prodrug compounds of Formula (I), and pharmaceutically acceptable salts, co-crystals, tautomers, stereoisomers, solvates, hydrates, polymorphs, and isotopically enriched derivatives thereof. Also provided are methods, uses, pharmaceutical compositions, and kits involving the inventive compounds or compositions for treating and/or preventing a disease and/or condition (e.g., inflammatory disease, infectious disease, pain) in a subject, optionally comprising illumination of the compound, composition, or pharmaceutical composition with light of an absorption wavelength sufficient to cleave the bonds between each instance of L and each instance of X upon illumination with the light (e.g., light between approximately 200 nm to 500 nm).

Abstract: The present disclosure provides compositions and methods for delivery of therapeutic agents across a barrier. The compositions include a therapeutic agent (e.g., antimicrobial agent, antibiotic), a permeation enhancer comprising sodium dodecyl sulfate, limonene, and/or bupivacaine which increases the flux of the therapeutic agent across the barrier, and a matrix forming agent that is a poloxamer (e.g., poloxamer P188), wherein the composition comprises: between about 0.2% and 3.2% wt/vol of a permeation enhancer that is sodium dodecyl sulfate; when present, between about 0.2% and 2.0% wt/vol of a permeation enhancer that is bupivacaine; between about 0.5% and 7.0% wt/vol of a permeation enhancer that is limonene; between approximately 18-62% P188; and the composition forms a gel at temperatures above a phase transition temperature that is less than about 37° C. The matrix forming agent forms a gel at a suitable gelation temperature and rheological properties for use in drug delivery.

Abstract: The present invention generally relates to particles such as nanoparticles and, in particular, to targeted nanoparticles. In some cases, the particles may have a targeting moiety that is inhibited from recognizing a target, for example, by being positioned within the particle at an internal location. The application of a stimulus, such as light, may allow the targeting moiety to interact externally of the particle. Accordingly, the particles may be targeted to specific locations using the application of a suitable stimulus. For instance, in one embodiment, particles containing cell-penetrating peptides attached via a first attachment and a second attachment containing a photocleavable entity may be administered to a subject, and light may be applied, e.g., to the eye, to cleave the photocleavable entity. However, despite the cleavage, the peptides remain associated with the particle via the first attachment, and thus, the particles may be able to penetrate cells within the eye due to peptides.

Abstract: Compositions and methods for administration of local anesthetics that are delivered by a single injection and enable repeated on-demand or high influx analgesia over extended periods have been developed. Pharmaceutical compositions including an effective amount of one or more sodium channel blockers including site 1 sodium channel blockers, optionally one or more alpha-2-adrenergic agonists, which are optionally encapsulated in liposomes, particles or microbubbles, and one or more triggerable elements are provided. The triggerable elements allow delivery of the encapsulated anesthetic drugs when an appropriate triggering stimuli are applied. Exemplary triggering agents or stimuli include near-infrared irradiation, UV- and visible light, ultrasound and magnetic field. In one embodiment, ultrasound is used to trigger a burst of microbubbles to enhance penetration of local anesthetic.

Abstract: The present invention provides compositions and methods for delivery of therapeutic agents across an barrier. The compositions include a therapeutic agent (e.g., antimicrobial agent, antibiotic, or anesthetic agent), a permeation enhancer which increases the flux of the therapeutic agent across the barrier, and a matrix forming agent. The matrix forming agent forms a gel at a suitable gelation temperature and rheological properties for use in drug delivery, and in some cases, the gelation temperature and rheological properties are not significantly changed from those of the composition without the permeation enhancer. The invention also provides a matrix forming agent and compositions thereof. Such compositions are particularly useful in the treatment of otitis media. Methods of treatment, methods of delivery, and kits for the compositions described herein are also provided.

Abstract: Compositions and methods of use related to formulations comprising anesthetics are generally described. Some embodiments are directed to compositions comprising a plurality of micelles and/or particles, and an anesthetic contained internally. These can be used to control and/or prolong the duration of IVRA while reducing the risk of systemic toxicity commonly due to administering anesthetics. The control and/or prolonged duration of IVRA may be due, at least in part, to the attachment of the sufficiently small micelles and/or particles to a biointerface (e.g., blood vessel surface) where the composition has been administered. Conventional IVRA methods commonly do not utilize potent and long-acting anesthetics (e.g., bupivacaine) due to the risks of cardiac toxicity. The compositions and methods described herein, however, provide a pathway for increased safety and efficiency of the use of such anesthetics, in certain embodiments. Resultantly, the performance (e.g.

Abstract: The present disclosure provides compositions and methods for delivery of therapeutic agents across a barrier. The compositions include a therapeutic agent (e.g., antimicrobial agent, antibiotic, or anesthetic agent), a permeation enhancer which increases the flux of the therapeutic agent across the barrier, and a matrix forming agent, wherein the composition comprises between about 0.5-5.0% wt/vol of a permeation enhancer that is sodium dodecyl sulfate; wherein the compositions comprise between about 0.5-2.5% wt/vol of a permeation enhancer that is bupivacaine; wherein the compositions comprise between about 1.5-12.0% wt/vol of a permeation enhancer that is limonene; and wherein the compositions comprise between about 9.0-19.0% wt/vol of a polymer that is poloxamer 407-poly(butoxy)phosphoester; and optionally further comprises between about 0.01-0.50% wt/vol of another therapeutic agent that is a sodium channel blocker anesthetic agent (e.g., tetrodotoxin).

Abstract: Anesthetics covalently conjugated onto biodegradable and biocompatible hydrophilic polymers via hydrolysable linkages provide controlled release of local anesthetics in vivo in an effective amount for nerve blockade with reduced toxicity relative to the unconjugated anesthetic agent. The rate of anesthetic release can be tuned by changing the hydrophilicity of the polymer. Exemplary formulations of Poly (glycerol sebacate) (PGS), optionally including Poly ethylene glycol (PEG) polymers conjugated to Tetrodotoxin (TTX) (PGS-PEG-TTX and PGS-TTX), and methods of use thereof are provided Nerve blockade from PGS-PEG-TTX and PGS-TTX was associated with minimal systemic and local toxicity to the muscle and the peripheral nerves. TDP-TTX conjugates homogeneously dispersed into PEG200 are also described. PEG200 not only worked as a medium, but also worked as a chemical permeation enhancer (CPE) to enhance the effectiveness of TTX.

Abstract: The present invention provides compositions and methods for delivery of therapeutic agents across an barrier. The compositions include a therapeutic agent (e.g., antimicrobial agent, antibiotic, or anesthetic agent), a permeation enhancer which increases the flux of the therapeutic agent across the barrier, and a matrix forming agent. The matrix forming agent forms a gel at a suitable gelation temperature and rheological properties for use in drug delivery, and in some cases, the gelation temperature and rheological properties are not significantly changed from those of the composition without the permeation enhancer. The invention also provides a matrix forming agent and compositions thereof. Such compositions are particularly useful in the treatment of otitis media. Methods of treatment, methods of delivery, and kits for the compositions described herein are also provided.

Abstract: The present invention generally relates to particles such as nanoparticles and, in particular, to targeted nanoparticles. In some cases, the particles may have a targeting moiety that is inhibited from recognizing a target, for example, by being positioned within the particle at an internal location. The application of a stimulus, such as light, may allow the targeting moiety to interact externally of the particle. Accordingly, the particles may be targeted to specific locations using the application of a suitable stimulus. For instance, in one embodiment, particles containing cell-penetrating peptides attached via a first attachment and a second attachment containing a photocleavable entity may be administered to a subject, and light may be applied, e.g., to the eye, to cleave the photocleavable entity. However, despite the cleavage, the peptides remain associated with the particle via the first attachment, and thus, the particles may be able to penetrate cells within the eye due to peptides.

Abstract: Compositions comprising polymers comprising one or more ketal, monothioketal, and/or thioketal bonds are provided, as well as related methods and kits. In some embodiments, a polymer may comprise one or more repeat units comprising one or more ketal, monothioketal, and/or thioketal bonds and a precursor of a pharmaceutically active agent. The precursor of the pharmaceutically active agent may be located in the backbone or may be a pendant group. The polymer may degrade in certain environments (e.g., aqueous environments, acidic environments, in vivo, etc.) to produce the pharmaceutically active agent and other biocompatible degradation products, such as certain ketones, alcohols, and/or thiols. Regardless of the location of the precursor of the pharmaceutically active agent in the repeat unit(s), the polymer may have a prolonged degradation time and/or release of the pharmaceutically active agent in certain environments.

Abstract: Nanoparticles as described herein are configured to bind to bacterial contaminants, such as Gram positive bacteria, Gram negative bacteria, and endotoxins. The nanoparticles include a core comprising a magnetic material; and a plurality of ligands attached to the core. The ligands include, for example, bis(dipicolylamine) (“DPA”) coordinated with a metal ion, e.g., Zn2+ or Cu2+, to form, e.g., bis-Zn-DPA or bis-Cu-DPA, which can bind to the bacterial contaminants. The nanoparticles can be included in compositions for use in methods and systems to separate bacterial contaminants from liquids, such as liquids, such as blood, e.g., whole or diluted blood, buffer solutions, albumin solutions, beverages for human and/or animal consumption, e.g., drinking water, liquid medications for humans and/or animals, or other liquids.

Abstract: Since each of the site I sodium channel blockers have a unique activity and cannot be used to extrapolate the same effective dosage for another site I sodium channel blocker, studies were conducted to identify dosages of neosaxitoxin (“NeoSTX”) and bupivacaine, alone or in combination with epinephrine, to provide two to three days of pain relief in humans. Bupivacaine-NeoSTX combinations produce more reliable blockade and longer duration blockade compared to NeoSTX alone. The three-way combination of NeoSTX-bupivacaine-epinephrine produces more prolonged local anesthesia than the two-way combination of NeoSTX-bupivacaine. Addition of epinephrine to this NeoSTX-bupivacaine combination dramatically prolongs the duration of complete blockade to a mechanical stimulus. These results led to development of specific combination dosage formulations.

Abstract: The present invention generally relates to systems and methods for targeted removal of a substance or biomolecule such as a protein from a biological fluid, such as blood. In some cases, the blood may be withdrawn from a subject, treated, and returned to the subject. Previous techniques for removal of biological materials from blood, such as hemodialysis and plasmapheresis, were generally non-specific (i.e., they removed a multitude of proteins/toxins from the blood). By contrast, novel methods and devices described herein are capable of removing specific or single substances such as proteins from biological fluids such as blood in a specific manner. Such highly specific protein removal has a broad array of clinical applications, including treatment of inflammatory conditions and autoimmune diseases.

Abstract: The present invention provides compositions and methods for delivery of therapeutic agents across an barrier. The compositions include a therapeutic agent (e.g., antimicrobial agent, antibiotic, or anesthetic agent), a permeation enhancer which increases the flux of the therapeutic agent across the barrier, and a matrix forming agent. The matrix forming agent forms a gel at a suitable gelation temperature and has rheological properties for use in drug delivery, and in some cases, the gelation temperature and rheological properties are not significantly changed from those of the composition without the permeation enhancer. The invention also provides a matrix forming agent and compositions thereof. Such compositions are particularly useful in the treatment of infectious disease (e.g., otitis media). Methods of treatment, methods of delivery, and kits for the compositions described herein are also provided.

Abstract: The present invention generally relates to systems and methods for targeted removal of a substance or biomolecule such as a protein from a biological fluid, such as blood. In some cases, the blood may be withdrawn from a subject, treated, and returned to the subject. Previous techniques for removal of biological materials from blood, such as hemodialysis and plasmapheresis, were generally non-specific (i.e., they removed a multitude of proteins/toxins from the blood). By contrast, novel methods and devices described herein are capable of removing specific or single substances such as proteins from biological fluids such as blood in a specific manner. Such highly specific protein removal has a broad array of clinical applications, including treatment of inflammatory conditions and autoimmune diseases.

Abstract: Compositions comprising polymers comprising one or more ketal, monothioketal, and/or thioketal bonds are provided, as well as related methods and kits. In some embodiments, a polymer may comprise one or more repeat units comprising one or more ketal, monothioketal, and/or thioketal bonds and a precursor of a pharmaceutically active agent. The precursor of the pharmaceutically active agent may be located in the backbone or may be a pendant group. The polymer may degrade in certain environments (e.g., aqueous environments, acidic environments, in vivo, etc.) to produce the pharmaceutically active agent and other biocompatible degradation f) products, such as certain ketones, alcohols, and/or thiols. Regardless of the location of the precursor of the pharmaceutically active agent in the repeat unit(s), the polymer may have a prolonged degradation time and/or release of the pharmaceutically active agent in certain environments.

Abstract: Nanoparticles as described herein are configured to bind to bacterial contaminants, such as Gram positive bacteria, Gram negative bacteria, and endotoxins. The nanoparticles include a core comprising a magnetic material; and a plurality of ligands attached to the core. The ligands include, for example, bis(dipicolylamine) (“DPA”) coordinated with a metal ion, e.g., Zn2+ or Cu2+, to form, e.g., bis-Zn-DPA or bis-Cu-DPA, which can bind to the bacterial contaminants. The nanoparticles can be included in compositions for use in methods and systems to separate bacterial contaminants from liquids, such as liquids, such as blood, e.g., whole or diluted blood, buffer solutions, albumin solutions, beverages for human and/or animal consumption, e.g., drinking water, liquid medications for humans and/or animals, or other liquids.