Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Novo Nordisk A/s

Tokitae LLC

The General Hospital Corporation

Harvard College

Entrega Inc.

Carlo Giovanni Traverso

Robert Samuel Langer

Andrew Bellinger

Shiyi Zhang

Alex G Abramson

Dean Liang Glettig

Lowell L Wood, Jr

Philip Andrew Eckhoff

Tyler Grant

Angela DiCiccio

Stacy Mo

Mousa Jafari

Ester Caffarel Salvador

Taylor Bensel

Minsoo Khang

Niclas Roxhed

Robert S Langer, Jr

Jorrit Jeroen Water

Malvika Verma

Ameya R Kirtane

Mette Poulsen

Junwei Li

Christoph Winfried Johannes Steiger

Yunhua Shi

Michael Scott Williams

Fadel Adib

George M Church

Daniel Griffith Anderson

Arthur J Coury

Thomas Henry Jozefiak

Christopher R Loose

Morten Revsgaard Frederiksen

Brian Jensen

Mikkel Oliver Jespersen

Jacob Wainer

Daniel Reker

David Dellal

Feyisope Eweje

Carl Magnus Schoellhammer

Yunfei Ma

Brian Mouridsen

Daniel Blankschtein

Zhihong Luo

Joshua Korzenik

Jacqueline Chu

Peter Herskind

Hen-Wei Huang

John Ashraf Fou Salama

Nhi Phan

Christoph Steiger

Sahab Babaee

Baris Erinc Polat

Bo Uldall Kristiansen

Hyunjoon Kim

Simo Pajovic

Jesper Peter Windum

Colin R Gardner

Anna I Mandinova

Albert Joseph Swiston

Canan Dagdeviren

Kerry Alexander Johnson

Avraham D Schroeder

Andreas Vegge

Sufeng Zhang

Robert Langer

Robert S Langer

Yi Lu

Tadd Bernard Hughes

Noah Davidsohn

Drago Sticker

Daniel Minahan

Ayush Verma

Avraham Schroeder

William Brugge

Yong Lin Kong

Ashok Kakkar

Denitsa M Milanova

Mikkel Wennemoes Hvitfeld Ley

Yida Zhao

Xiaoya Lu

Torben Sebastian Last

Graham Arrick

Siheng You

Jiaqi Lin

Cody Cleveland

Michael Williams

Vance Soares

Jason Siu Wei Li

Thomas Wang

Gary W Liu

Jacob Coffey

Grace Junyue Zhong

Netra Rajesh

Omar Abouzid

Lewis Scott Jones

Declan Gwynne

Miguel Jimenez

The present disclosure provides a kirigami-inspired injectable stent system. The stent systems and methods enable radial/circumferential and longitudinal delivery of an extended release of therapeutics within tubular structures of the body, such as the GI tract and trachea. According to some aspects, a kirigami-based injectable stent system is provided that can enable drug release through deposition of therapeutic-coated needles of the stent in the tubular mucosa, such as often found in the gastrointestinal tract or trachea.

Kirigami-inspired stents for sustained local delivery of therapeutics

The present disclosure provides branched poly(β-amino esters) (PBAEs) of Formula (I) made by reacting primary amines with diacrylates. Further provided herein are compositions comprising the polymers of Formula (I), and methods of using the compositions and polymers as described herein for the treatment of disease.L-(R)  (I)

Branched poly(-amino esters) for the delivery of nucleic acids

Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the article may be configured to control drug release e.g., with zero-order drug kinetics with no potential for burst release for weeks to months. In some embodiments, the articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the article includes dimensions configured for transesophageal retrieval. In some cases, the articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).

Resident articles for gram-level dosing

The disclosure describes poly(β-thioester) polymers and polymeric nanoparticles, pharmaceutical compositions comprising these materials, their use in the treatment of cancer and infectious disease, and machine learning methods for identifying and selecting them.

Poly(beta-thioester) polymers and polymeric nanoparticles

Self-actuating articles including, for example, self-actuating needles and/or self-actuating biopsy punches, are generally provided. Advantageously, the self-actuating articles described herein may be useful as a general platform for delivery of a wide variety of pharmaceutical drugs that are typically delivered via injection directly into tissue due to degradation in the GI tract. The self-actuating articles described herein may also be used to deliver sensors and/or take biopsies without the need for an endoscopy. In some embodiments, the article comprises a spring (e.g., a coil spring, a beam, a material having particular mechanical recovery characteristics). Those of ordinary skill in the art would understand that the term spring is not intended to be limited to coil springs, but generally encompass any reversibly compressive material and/or component which, after releasing an applied compressive force on the material/component, the material/component substantially returns to an uncompressed length of the material/component (e.g., the within 95% of the length of the material/component prior to compression).

Self-actuating articles

Systems and methods related to reconfigurable medical devices are described. In some embodiments, a reconfigurable medical device may include a central core and a plurality of arms. The arms may be rotatably coupled to the central core such that the plurality of arms may rotate outwards away from the central core to selectively reconfigure the reconfigurable device between a retracted configuration and an expanded configuration. In an initial state, the arms may be biased outwards away from the central core into the expanded configuration. When the reconfigurable device is exposed to a temperature greater than a threshold temperature, the arms may be biased towards the central core into the retracted configuration. In some embodiments, a reconfigurable medical device may include therapeutic compound-loaded needles coupled to distal portions of the arms.

Thermally controlled reconfigurable medical devices

Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface. In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent. In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent.

Self-righting systems, methods, and related components

Articles and methods for delivering a therapeutic agent to a subject are described. These articles and methods may be useful, in some cases, for the delivery of therapeutic agents to the colon of a subject. In some embodiments, an article is configured to release a secretion inducing agent e.g., to stimulate the release of intestinal fluids. The article, in some embodiments, comprises a therapeutic agent such that the stimulated release of intestinal fluid increases the amount of therapeutic agent available for absorption by the colon. For example, in some embodiments, the articles and methods described herein advantageously promote increased absorption of therapeutic agents in subjects as compared to traditionally administered therapeutic agents without additional components such as a secretion inducing agent. In some embodiments, articles and methods described herein may increase the motility of the colon of a subject. The increase in contractions and movement of fluidic in the colon caused by increase motility may advantageously facilitate the dissolution or absorption of the therapeutic agent.

Articles and methods for administration of therapeutic agents

Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the residence articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the residence article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the residence article may be configured to control drug release e.g., with zero-order drug kinetics with no potential for burst release for weeks to months. In some embodiments, the residence articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the residence article includes dimensions configured for transesophageal retrieval. In some cases, the residence articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).

Gastroretentive articles for alcohol sensing

A drug delivery device for administration to a subject is provided. In some embodiments, the drug delivery device includes a reservoir containing an active pharmaceutical ingredient and a potential energy source. The drug delivery device also includes a trigger operatively associated with the potential energy source, where the trigger is configured to actuate at a predetermined location within the subject. The drug delivery device also includes a rupturable membrane disposed along a flow path extending between the reservoir and an outlet, where the membrane is configured to rupture when the trigger is actuated. Once the trigger is actuated, the potential energy from the potential energy source may be released to expel the active pharmaceutical ingredient in a jet through the outlet.

Drug delivery device

Components with relatively high loading of active pharmaceutical ingredients (e.g., drugs), are generally provided. In some embodiments, the component (e.g., a tissue interfacing component) comprises a solid therapeutic agent (e.g., a solid API) and a supporting material (e.g., a binder such as a polymer) such that the solid therapeutic agent is present in the component in an amount of greater than or equal to 10 wt % versus the total weight of the tissue interfacing component. Such tissue-interfacing components may be useful for delivery of API doses e.g., to a subject. Advantageously, in some embodiments, the reduction of volume required to deliver the required API dose as compared to a liquid formulation permits the creation of solid needle delivery systems for a wide variety of drugs in a variety of places/tissues (e.g., tongue, GI mucosal tissue, skin) and/or reduces and/or eliminates the application of an external force in order to inject a drug solution through the small opening in the needle. In some cases, a physiologically relevant dose may be present in a single tissue interfacing component (e.g., having a relatively high API loading).

Components with high API loading

Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one 5 or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In certain embodiments, the self-righting article a tissue 10 interfacing components. In some embodiments, each tissue-interfacing component may comprise an electrically-conductive portion configured for electrical communication with tissue and an insulative portion configured to not be in electrical communication with tissue.

Systems for electrical stimulation

Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject). In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component is associated with a self-actuating component. For example, the self-righting article may comprise a self-actuating component configured, upon exposure to a fluid, to release the tissue interfacing component from the self-righting article. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent (e.g., for delivery to a location internal to a subject).

Self-righting systems and related components and methods

Methods and compositions for determining multiplex interactions between drugs and drug transporters using an intestinal tissue explant are provided.

Ex vivo system for determining multiple drug-drug transporter interactions and methods of use thereof

The present disclosure provides compositions, methods, and kits that enable the in situ growth of polymers on or within a subject. In some aspects, the monomer, dopamine, polymerizes in vivo to form a polymer on a tissue. In additional aspects, the compositions, methods, and kits are useful for treating or preventing a disease or disorder.

Tissue catalyzed growth of polymer as epithelial linings for therapy

Growing community of inventors

Newton, MA, United States of America

Carlo Giovanni Traverso