Abstract: A device configured to be implanted in a subject includes a sensing module, a therapeutic module, and a battery. The sensing module includes at least two of an accelerometer, an electrocardiogram (ECG) sensor, a photoplethysmogram (PPG) sensor, and a temperature sensor. The therapeutic module includes a drug reservoir and a reciprocating pump. The battery powers the sensing module and the therapeutic module. The sensing module is configured to detect a biological event in the subject and, upon detection of the biological event, send a signal to the therapeutic module. The therapeutic module is configured to receive the signal from the sensing module and, upon receiving the signal, administer a drug to the subject from the drug reservoir via the pump.

Abstract: A system for assessing a pressure profile of a gastrointestinal (GI) tract is provided. The system includes a flexible tube defining a first lumen and an electrically-conductive liquid contained within the first lumen. At least one restriction is restriction formed on the flexible tube to constrict but not completely occlude the first lumen. The system further includes a sensor system configured to monitor an electrical property of the electrically-conductive fluid over time and to generate a report of pressure changes in the GI tract by correlating changes in the electrical property with the pressure changes in the GI tract.

Abstract: 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.

Abstract: A device is configured to be administered via an oral route by a subject. The device includes an anode, a seal disposed on the anode, and a cathode. When exposed to a liquid or a hydrogel, an exposed surface of the anode undergoes galvanic oxidation dissolution to provide DC power to the device. As the exposed surface of the anode undergoes galvanic oxidation dissolution, the seal incrementally detaches from the anode, and a substantially constant surface area of the exposed surface is maintained.

Abstract: Tissue explants of the gastrointestinal tract are provided. Methods of making and using the tissue explants are also provided, along with substrates designed for the tissue explants described.

Abstract: Insulin therapy revolutionized the care of patients with diabetes, yet insulin-induced hypoglycemia remains a serious life-threatening complication of insulin therapy. Glucagon is a highly effective treatment for hypoglycemia; however, current dosage forms remain under-utilized due to poor patient compliance. High-density, readily soluble, and thermostable solid glucagon formulations applied with painless, application-specific microneedle-patches can treat hypoglycemia in type 1 diabetes patients who are awake or asleep. On-demand patches can prevent or treat mild hypoglycemia during the day, and enzyme-driven hypoglycemia-responsive patches can release glucagon autonomously during the night. These patches have excellent in vitro glucagon stability, loading, and release kinetics and can treat hypoglycemia in diabetic humans and animals. These delivery systems enable new modes of glucagon therapy, thereby expanding the clinical role of glucagon beyond the emergency setting.

Abstract: 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.

Abstract: 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).

Abstract: 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.

Abstract: An ingestible device may include one or more deployable limbs configured to orient the ingestible device in a desired orientation. The one or more limbs may be attached to body of the device and wrap around the device in an initial configuration (e.g., prior to deployment of the one or more limbs). The one or more limbs may be configured to deploy when exposed to a predetermined condition. Once the predetermined condition is met, the one or more limbs may extend outwards away from the body such that the one or more deployed limbs serve to orient the ingestible device.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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).

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

Abstract: 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 tissue-active monomers, including monomers comprising macromolecules, provide a broad set of material choices for synthetic tissue barriers. In additional aspects, the compositions, methods, and kits are useful for treating or preventing a disease or disorder.

Abstract: 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.

Abstract: 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).

Abstract: A method for the systemic delivery of a polypeptide within a subject is provided by creating genetically modified skin cells via topical introduction of a genetically engineered virus which delivers a nucleic acid encoding a therapeutic polypeptide for expression by the skin cells, wherein the expressed therapeutic polypeptide is secreted by the skin cells and is introduced into the circulatory system of the subject.

Abstract: 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).