Children's Medical Center Corporation

Massachusetts Institute of Technology

Harvard College

Other

The General Hospital Corporation

Columbia University

Pepsico, Inc.

Boston University

Massachusetts Eye and Ear Infirmary

Children's Hospital Boston

Whitehead Institute

Daniel S Kohane

Robert Samuel Langer

Charles B Berde

Tal Dvir

Charles M Lieber

Bozhi Tian

Jia Liu

Rong Yang

Jung-Jae Lee

Kyung Jae Jeong

Emmanuel John Simons

Lily Yun Lin

Todd R Hoare

Itay Sagie

Peter S Given

Gerald R Fink

Yoon Yeo

Mark A Borden

Robert S Langer, Jr

Christiaan Nijst

Ifat Rubin-Bejerano

Joost P Bruggeman

Lino Da Silva Ferreira

Jason Fuller

Wei Zhang

Robert S Langer

Joseph B Ciolino

Yanfei Wang

Robert Langer

Claudia Abeijon

Brian Timko

Shutao Guo

Gary Strichartz

Yueqin Zheng

Changyou Zhan

Hila Epstein-Barash

Kathleen J Cullion

Sahadev Aramanethalgur Shankarappa

Alina Y Rwei

Aoune Barhoumi

Boaz Mizrahi

Ryan G Wylie

James B McAlvin

Chao Zhao

Matthew Ryan Banghart

Charles Berde

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.

Local anesthetics with selective-sensory nerve blockade

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).

Macromolecular prodrugs for light-emitting diodes and uses thereof

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.

Compositions with permeation enhancers for drug delivery

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. Other aspects are generally directed to methods of making or using such particles, kits involving such particles, or the like.

Nanoparticles for treatment of choroidal neovascularization and other indications

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.

Compositions and methods for on-demand high-efficiency triggerable anesthesia

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. Various compositions, described herein, may be particularly well suited for applications requiring extended release of pharmaceutically active agents, such as the treatment of ophthalmic disorders.

Poly(ketals) and related compositions and methods

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., Znor Cu, 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.

Magnetic separation using nanoparticles

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.

Neosaxitoxin combination formulations for prolonged local anesthesia

The present invention generally relates to nanoscale wires and tissue engineering. In various embodiments, cell scaffolds for growing cells or tissues can be formed that include nanoscale wires that can be connected to electronic circuits extending externally of the cell scaffold. The nanoscale wires may form an integral part of cells or tissues grown from the cell scaffold, and can even be determined or controlled, e.g., using various electronic circuits. This approach allows for the creation of fundamentally new types of functionalized cells and tissues, due to the high degree of electronic control offered by the nanoscale wires and electronic circuits. Accordingly, such cell scaffolds can be used to grow cells or tissues which can be determined and/or controlled at very high resolutions, due to the presence of the nanoscale wires, and such cell scaffolds will find use in a wide variety of novel applications, including applications in tissue engineering, prosthetics, pacemakers, implants, or the like.

Scaffolds comprising nanoelectronic components for cells, tissues, and other applications

Injectable or implantable drug delivery systems providing on-demand ultrasound-triggered drug release and methods for controlling the release of drug in a patient are provided herein. The on-demand drug delivery systems contain a drug depot and a drug encapsulated in an encapsulating material, where the encapsulating material is different from the depot. In the preferred embodiment, the depot also contains microbubbles that encapsulate one or more gases. The microbubbles enhance the drug release when ultrasound is applied compared to the same system in the absence of microbubbles. In a preferred embodiment, the drug delivery system, contains an encapsulating material, preferably liposomes, a drug to be delivered, microbubbles, and at least two hydrogel-forming precursor components. Following injection or implantation, the patient can control the time, location and dosage released by administering ultrasound.

Composition for on-demand ultrasound-triggered drug delivery

This invention is directed to &#x3b2;-1-6-glucans, compositions and devices comprising the same, and methods of use thereof in modulating immune responses. The &#x3b2;-1-6-glucans of certain embodiments of the invention are enriched for O-acetylated groups and/or conjugated to a solid support or linked to a targeting moiety.

Immunomodulating compositions and methods of use thereof

Growing community of inventors

Newton, MA, United States of America

Daniel S Kohane