Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Lyndra Therapeutics, Inc.

Tokitae LLC

Andrew Bellinger

Carlo Giovanni Traverso

Tyler Grant

Robert Samuel Langer

Shiyi Zhang

Dean Liang Glettig

Lowell L Wood, Jr

Philip Andrew Eckhoff

Angela DiCiccio

Stacy Mo

Mousa Jafari

Rosemary Lynn Kanasty

Stephen E Zale

Colin R Gardner

Nupura Bhise

Jung Hoon Yang

James I Wright

Susan C Low

Bennett Carter

Robert S Langer

Philip A Eckhoff

Lowell L Jr Wood

Robert S Langer, Jr

Taylor Bensel

Malvika Verma

Ameya R Kirtane

Daniel Minahan

David Altreuter

Saumya Moorthy

Jiaqi Lin

Omar Abouzid

Robert Debenedictis

John Klier

Angela Diciccio

Rosemary Kanasty

Colin Gardner

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 invention provides gastric residence systems with specifically tailored architectures and methods for making such systems. The components of the gastric residence systems can be manufactured by three-dimensional printing or by co-extrusion. The ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the systems.

Materials architecture for gastric residence systems

The invention provides gastric residence systems, or components of gastric residence system such as segments or elongate members of gastric residence systems, with release rate-modulating films and methods for making and using such systems. The release rate-modulating films provide good control over release of agents (such as therapeutic, diagnostic, or nutritional agents) present in the gastric residence system. The films also permit higher drug loading in the gastric residence systems and components of gastric residence systems while maintaining good control over release of agents. Some embodiments of the films can provide resistance against burst release of agent upon exposure to alcohol.

Gastric residence systems with release rate-modulating films

The invention provides gastric residence systems with configurations and geometrical dimensions that allow for improved shelf life during prolonged storage, and optimal residence properties when the systems are deployed in the stomach of a patient.

Geometric configurations for gastric residence systems

The invention provides gastric residence systems for administration of adamantane-class drugs or pharmaceutically acceptable salts thereof, such as memantine or pharmaceutically acceptable salts thereof, and methods for making and using such systems. The systems provide extended release of drug, reducing the frequency with which the drug must be administered to the patient. The gastric residence systems, or components of gastric residence system such as segments or elongate members of gastric residence systems, can have release rate-modulating films, which provide good control over release of adamantane-class drugs or pharmaceutically acceptable salts thereof present in the gastric residence system. Some embodiments of the films can provide resistance against burst release of adamantane-class drugs or pharmaceutically acceptable salts thereof upon exposure to alcohol.

Gastric residence systems for sustained delivery of adamantane-class drugs

Gastric residence systems comprising therapeutic agent formulations for sustained gastric release of therapeutic agents are disclosed, as well as methods for using such systems. The systems are characterized by use of a dispersant in the formulations, which improves the burst release characteristics and long-term release rate characteristics of the systems. Milling of therapeutic agent can also be performed to prepare agent particles of desired size.

Gastric residence systems for sustained release of therapeutic agents and methods of use thereof

Certain embodiments comprise administering a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance, and, optionally, a linker. In some such embodiments, the linker may be configured to degrade.

Residence structures and related methods

Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.g., ingestion of a solution that induces rapid dissolution/degradation). In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance (e.g., a therapeutic agent), and, optionally, a linker. In some such embodiments, the linker may be configured to degrade such that the residence structure breaks apart and is released from the location internally of the subject after a predetermined amount of time.

Enteric elastomers and related methods are generally provided. In some embodiments, the enteric elastomer is a polymer composite. Certain embodiments comprise a polymer composite in which hydrogen bonds within two carboxyl group-containing polymers cross-link the polymer networks into an elastic and pH-responsive polymer composite. Advantageously, this polymer composite has the capacity of being stable and elastic in an acidic environment such as that of the stomach but can be dissolved in a neutral pH environment such as that of the small and large intestines. In some embodiments, the polymer composites described herein comprise a mixture of two or more polymers with carboxyl functionality such that the two or more polymers form hydrogen bonds. In certain embodiments, the polymer composite has both enteric and elastic properties.

Enteric elastomers

Residence devices as well as their related methods of manufacture and use are generally provided. In some embodiments, a residence device includes a plurality of self-assembling structures that assemble in vivo to form an aggregate structure. Each structure of the plurality of structures includes a first side and a first attachment point that attaches to a second attachment point on another structure of the plurality of structures. The aggregate structure may be sized and shaped to maintain an in vivo position relative to an internal orifice of a subject. The attachment between the first and second attachment points may degrade after a period of time.

Self-assembled residence devices and related methods

Certain embodiments involve administering a residence structure to a subject (e.g., a patient) in a constrained configuration, then unconstraining the structure such that it is retained at a location internally of the subject for a period of time. The structure includes a loadable component that can carry an active substance for release internally of the subject.

Certain embodiments involve gastric residence structures which can be administered to a subject (e.g., a patient) in a configuration constrained by a retaining element, and configured to mediate a change in shape when unconstrained by the retaining element to assume a configuration in the stomach in which is retained and unable to pass through the gastric pyloric orifice of the subject under gastrointestinal physiological conditions. The residence structures can be loaded with an agent for release in the stomach.

Growing community of inventors

Wellesley, MA, United States of America

Andrew Bellinger