Ingestible devices, assemblies, and methods for delivering therapeutic formulations within the gastrointestinal tract

Abstract

An ingestible device for delivering a therapeutic formulation into a luminal wall or into surrounding tissue of a gastrointestinal (GI) tract of a subject includes a housing, a support, an arm, a delivery assembly, a stretcher, an actuator, and a release means. The support is disposed within the housing and defines a longitudinal axis of the device. The delivery assembly includes a delivery structure coupled to the arm and a therapeutic formulation disposed within the delivery structure. The stretcher is coupled to at least one of the support or the delivery assembly. The stretcher is a structure that extends along the longitudinal axis to substantially align the delivery structure with respect to the luminal wall. The actuator is coupled to the delivery assembly. The release means is coupled to the actuator and is actuated in response to conditions within the GI tract to cause actuation of the actuator. When the release means is actuated, the actuator pivots the arm relative to the support such that the delivery assembly extends outward from the longitudinal axis toward the luminal wall to deliver the therapeutic formulation from the delivery structure into the luminal wall or into surrounding tissue.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of and priority to U.S. Provisional Application No. 63 / 317,798, filed March 8, 2022, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] Generally speaking, therapeutic agents, such as drugs, can be administered to a subject by ingestion or parenteral injection (e.g., subcutaneously, intramuscularly, intravenously) to provide a desired therapeutic effect. However, these routes of administration have several drawbacks. For example, some therapeutic agents, such as large (macro) molecules, are not suitable for delivery by ingestion due to enzymatic degradation of these molecules in the gastrointestinal (GI) tract of the subject. Other types of therapeutic agents are poorly tolerated in the GI tract and have low systemic uptake. In the case of parenteral injections, subjects experience pain and inconvenience associated with administration, which can significantly impact compliance and quality of life.

[0003] Thus, there is a need for improved devices, assemblies, and methods for delivering therapeutic agents to the GI tract that address one or more of the above-mentioned shortcomings. Summary of the Invention [Problem to be solved by the invention]

[0004] SUMMARY OF THE DISCLOSURE Embodiments of the present disclosure relate generally to ingestible devices, assemblies, and methods for effectively delivering one or more therapeutic agents into the GI tract lumen wall or surrounding tissues (eg, the peritoneum or peritoneal cavity) of a subject. [Means for solving the problem]

[0005] In one aspect, an ingestible device for delivering a therapeutic formulation into a luminal wall or surrounding tissue of a subject's GI tract includes a housing, a support, an arm, a delivery assembly, an extender, an actuator, and a release. The support is disposed within the housing and defines a longitudinal axis of the device. The delivery assembly includes a delivery structure coupled to the arm and a therapeutic formulation disposed within the delivery structure. The extender is coupled to at least one of the support or the delivery assembly. The extender is a structure that extends along the longitudinal axis to substantially align the delivery structure with respect to the luminal wall. The actuator is coupled to the delivery assembly. The release is coupled to the actuator and is actuated in response to conditions within the GI tract to cause actuation of the actuator. In one or more embodiments, when the release is actuated, the actuator pivots the arm relative to the support such that the delivery assembly extends outward from the longitudinal axis toward the luminal wall to deliver the therapeutic formulation from the delivery structure into the luminal wall.

[0006] In another aspect, a delivery assembly for delivering a therapeutic formulation into a luminal wall or surrounding tissue of a subject's GI tract includes a delivery structure and a therapeutic formulation. The delivery structure is a structure coupled to the arm and includes the therapeutic formulation therein. The delivery assembly is a structure that extends outwardly away from the support such that the delivery structure is positioned adjacent to or in contact with a surface of the luminal wall. The delivery assembly is configured to expel the therapeutic formulation from the delivery structure into the luminal wall.

[0007] In another aspect, a method of delivering a therapeutic formulation into a luminal wall or surrounding tissue of a subject's GI tract includes administering to the subject an ingestible device, the ingestible device including a housing, a support, an arm, a delivery assembly, a stretcher, an actuator, and a release means. The support defines a longitudinal axis of the device. The arm is pivotally coupled to the support. The delivery assembly includes a delivery structure coupled to the arm and a therapeutic formulation disposed within the delivery structure. The stretcher is coupled to at least one of the support or the delivery assembly. The actuator is coupled to the delivery assembly. The release means is coupled to the actuator. The actuator is actuated in response to actuation of the release means. The stretcher extends along the longitudinal axis to align the delivery structure with respect to the luminal wall upon actuation of the actuator. The arm pivots relative to the support such that the delivery assembly extends outwardly away from the longitudinal axis toward the luminal wall. The therapeutic formulation is expelled from the delivery structure into the luminal wall or surrounding tissue.

[0008] In one or more embodiments of the aforementioned aspect, the actuator is configured to generate an axial force along the longitudinal axis to pivot the arm.

[0009] In one or more embodiments of the aforementioned aspect, the actuator is configured to generate a rotational force about the longitudinal axis to pivot the arm.

[0010] In one or more embodiments of the aforementioned aspect, the support includes a plurality of sections movably coupled to one another to define an extended configuration, and upon actuation of the release means, the plurality of sections move relative to one another such that the support extends axially along the longitudinal axis.

[0011] In one or more embodiments of the aforementioned aspect, the actuator is coupled to the delivery assembly and the stretcher such that, when the release means is actuated, the actuator substantially simultaneously stretches the delivery assembly outwardly away from the longitudinal axis and stretches the stretcher along the longitudinal axis.

[0012] In one or more embodiments of the aforementioned aspect, the housing defines an interior, and the support, the arm, the delivery assembly, the extender, the actuator, and the release means are disposed within the interior.

[0013] In one or more embodiments of the aforementioned aspect, the housing is structured as a capsule including a first segment and a second segment, the first segment being removably coupled to the second segment, and at least one of the actuator, support, or stretcher configured to push apart the first and second segments.

[0014] In one or more embodiments of the aforementioned aspect, the release means is a first release means and the actuator is a first actuator. The delivery structure further includes a second release means operably coupled to a second actuator for actively delivering the therapeutic compound. The second release means is configured to cause the second actuator to expel the therapeutic compound from the delivery structure into the GI lumen wall or into the surrounding tissue after the first actuator causes the delivery assembly to extend outwardly away from the support.

[0015] In one or more embodiments of the aforementioned aspect, the second release means is selectively exposed to fluid within the GI lumen in response to movement of the delivery assembly to actuate the second release means.

[0016] In one or more embodiments of the aforementioned aspect, the second release means is selectively moved in response to movement of the delivery assembly to actuate the second release means.

[0017] In one or more embodiments of the aforementioned aspect, the first release means has a first degradation rate and the second release means has a second degradation rate, the second degradation rate being less than the first degradation rate.

[0018] In one or more embodiments of the aforementioned aspect, the delivery structure includes a holder coupled to the arm and a container coupled to the holder, the container configured to contain the therapeutic formulation therein.

[0019] In one or more embodiments of the preceding aspect, the container includes a body, a first seal, and a second seal. The body includes a first open end, a second open end opposite the first open end, and a sidewall defining an interior for containing the therapeutic formulation. The first seal is joined at the first open end and the second seal is joined at the second open end to substantially seal the interior.

[0020] In one or more embodiments of the foregoing aspect, the holder includes a protrusion disposed within an interior portion of the holder. The container is slidably coupled to and at least partially disposed in the interior portion of the holder adjacent the protrusion. The delivery structure is configured such that when the container contacts the luminal wall in response to the delivery assembly extending outwardly away from the longitudinal axis, the container moves inwardly toward the protrusion, causing the protrusion to expel the therapeutic formulation from the container into the luminal wall.

[0021] In one or more embodiments of the aforementioned aspect, the holder defines a piston chamber and the delivery structure includes a piston slidably disposed within the piston chamber.

[0022] In one or more embodiments of the aforementioned aspect, the holder further defines a reaction chamber and the delivery structure further includes an igniter, a charge, and an electrical circuit. The igniter and the charge are disposed within the reaction chamber. The electrical circuit is operatively coupled to the igniter. The igniter ignites the charge in response to a signal received from the electrical circuit, generating a force within the reaction chamber that causes the piston to expel the therapeutic formulation from the container and into the lumen wall.

[0023] In one or more embodiments of the aforementioned aspects, the holder further defines a reaction chamber, and the delivery structure further includes a first reactant disposed in the reaction chamber, a second reactant disposed in the piston chamber below the piston, and a release mechanism coupled to the holder. When the release mechanism is actuated, the reaction chamber is fluidly coupled to the piston chamber, mixing the first reactant with the second reactant to cause a chemical reaction and generating a force that causes the piston to expel the therapeutic formulation from the container toward the lumen wall.

[0024] In one or more embodiments of the aforementioned aspect, the delivery structure further includes a spring coupled to the piston and a release mechanism coupled to the spring, wherein actuation of the release mechanism causes the spring to expand and cause the piston to expel the therapeutic formulation from the container to the lumen wall.

[0025] In one or more embodiments of the aforementioned aspects, the delivery structure includes a retention feature for temporarily retaining the delivery structure against the lumen wall.

[0026] In one or more embodiments of the aforementioned aspects, the device further includes a plurality of arms pivotally coupled together in a cross shape to define a scissor mechanism, the arm being one of the plurality of arms. One or more of the plurality of arms may be slidably coupled to the support.

[0027] In one or more embodiments of the aforementioned aspect, the actuator includes a spring that is held in a compressed state by a primary release means and that upon actuation of the release means expands along the longitudinal axis to pivot the arm relative to the support.

[0028] In one or more embodiments of the aforementioned aspect, the actuator includes an expandable member. The expandable member also functions as a stretcher. The expandable member includes a plurality of reactants disposed therein, the reactants being temporarily separated from one another by a releasing means. The releasing means is coupled to the expandable member, such that upon actuation of the releasing means, the plurality of reactants mix and undergo a chemical reaction within the expandable member, generating a gas that inflates the expandable member, thereby pivoting the arm relative to the support.

[0029] In one or more embodiments of the aforementioned aspect, the actuator includes a housing defining a piston chamber, and the support includes a piston slidably disposed within the piston chamber.

[0030] In one or more embodiments of the aforementioned aspect, the housing further defines a reaction chamber, and the actuator further includes an igniter, a charge disposed in the reaction chamber, and an electrical circuit operably coupled to the igniter. Upon actuation of the release means, the electrical circuit generates a signal that causes the igniter to ignite the charge, generating a force in the reaction chamber to move the piston and support along the longitudinal axis relative to the housing, thereby pivoting the arm relative to the support.

[0031] In one or more embodiments of the aforementioned aspect, the actuator further comprises a hydrogel disposed within the piston chamber. The release means is coupled to the housing. The housing comprises a plurality of openings for providing a fluid pathway between the chamber and the GI lumen environment. Upon actuation of the release means, fluid from the GI lumen environment enters the chamber through one or more of the plurality of openings and expands the hydrogel within the chamber to move the piston and the support, thereby pivoting the arm relative to the support.

[0032] In one or more embodiments of the aforementioned aspect, the actuator includes a motor. The motor is a rotary motor, and the support includes a threaded portion rotatably coupled to the rotary motor. The release means is disposed on an electrical contact of the motor, and upon actuation of the release means, an electrical short is created across the electrical contact, causing the motor to rotate the support relative to the motor, causing the support to translate along the longitudinal axis, and thereby causing the arm to pivot relative to the support.

[0033] In one or more embodiments of the aforementioned aspects, the device further comprises a plurality of delivery assemblies pivotally coupled to the support.

[0034] The foregoing general description and the following detailed description are provided by way of example only and are intended to provide further explanation of the present disclosure as set forth in the claims, without limiting the scope of the disclosure or the claims. Other objects, advantages, and novel features will be readily apparent to those skilled in the art from the following brief description of the drawings and detailed description of the present disclosure. [Brief description of the drawings]

[0035] [Figure 1] FIG. 1 illustrates a block diagram of one embodiment of an ingestible device. [Figure 2A] 2A shows a cross-section of one embodiment of an ingestible device in the form of a capsule. The device is shown in a first state before the device reaches a desired location in the GI tract to deliver a therapeutic formulation. [Figure 2B] FIG. 2B shows the device of FIG. 2A in a second state after it has reached a desired location within the GI tract. [Figure 3A] 3A shows a cross-section of one embodiment of an ingestible device including an actuator in the form of a spring. The device is shown in a first state before the device reaches a desired location in the GI tract to deliver a therapeutic formulation. [Figure 3B] FIG. 3B shows the device of FIG. 3A in a second state after the device has reached a desired location within the GI tract. [Figure 4A] 4A shows a cross-section of an embodiment of an ingestible device including an actuator in the form of an expandable member. The device is shown in a first state before the device reaches a desired location in the GI tract to deliver a therapeutic formulation. [Figure 4B] FIG. 4B shows the device of FIG. 4A in a second state after the device has reached a desired location within the GI tract. [Figure 5A] 5A shows a cross-section of an embodiment of an ingestible device that includes an actuator in the form of a piston, an igniter, and a charge. The device is shown in a first state before the device reaches a desired location in the GI tract to deliver a therapeutic formulation. [Figure 5B] FIG. 5B shows a cross-section of the device of FIG. 5A in a second state after the device has reached a desired location within the GI tract. [Figure 6A] 6A shows a cross-section of one embodiment of an ingestible device including an actuator in the form of a rotary motor. The device is shown in a first state before the device reaches a desired location in the GI tract to deliver a therapeutic formulation. [Figure 6B] FIG. 6B shows the device of FIG. 6A in a second state after the device has reached a desired location within the GI tract. [Figure 7A] 7A shows a cross-section of one embodiment of an ingestible device comprising a piston-shaped actuator and a hydrogel, the device being shown in a first state before the device reaches a desired location in the GI tract to deliver a therapeutic formulation. [Figure 7B] FIG. 7B shows the device of FIG. 7A in a second state after the device has reached a desired location within the GI tract. [Figure 8A] 8A shows a cross-section of one embodiment of an ingestible device including a pivotable arm. The device is shown in a first state before the device reaches a desired location in the GI tract to deliver a therapeutic formulation. [Figure 8B] FIG. 8B shows the device of FIG. 8A in a second state after the device has reached a desired location within the GI tract. [Figure 9A] 9A shows a cross-section of one embodiment of an ingestible device including a pivotable arm and a movable wedge. The device is shown in a first state before the device reaches a desired location in the GI tract to deliver a therapeutic formulation. [Figure 9B] FIG. 9B shows the device of FIG. 9A in a second state after the device has reached a desired location within the GI tract. [Figure 10A] 10A shows a cross-section of one embodiment of a delivery structure including protrusions for delivering a therapeutic compound into the luminal wall of the GI tract. The delivery structure is shown in a first state prior to delivering the therapeutic compound. [Figure 10B] FIG. 10B shows the delivery structure of FIG. 10A in a second state after the protrusions have expelled the therapeutic compound from the delivery structure and into the lumen wall. [Figure 11A] 11A shows a cross-section of an embodiment of a delivery structure including a piston, an igniter, and a charge for actively delivering a therapeutic compound into the luminal wall of the GI tract. The delivery structure is shown in a first state prior to delivery of the therapeutic compound. [Figure 11B] FIG. 11B shows the delivery assembly of FIG. 11A in a second state after the piston has expelled the therapeutic compound from the delivery structure and into the lumen wall. [Figure 12A] 12A shows a cross-section of an embodiment of a delivery structure including a spring and a piston for actively delivering a therapeutic compound into the luminal wall of the GI tract. The delivery structure is shown in a first state prior to delivering the therapeutic compound. [Figure 12B] FIG. 12B shows the delivery structure of FIG. 12A in a second state after the piston has expelled the therapeutic compound from the delivery structure and into the lumen wall. [Figure 13A] 13A shows a cross-section of an embodiment of a delivery structure including multiple reactants and a piston for actively delivering a therapeutic compound into a luminal wall of the GI tract. The delivery structure is shown in a first state prior to delivering the therapeutic compound. [Figure 13B] FIG. 13B shows the delivery structure of FIG. 13A in a second state after the piston has expelled the therapeutic compound from the delivery structure and into the lumen wall. [Figure 14A] 14A is a front cross-sectional view of an ingestible device including multiple delivery assemblies, shown in a first state before the device reaches a desired location in the GI tract to deliver a therapeutic formulation. [Figure 14B] FIG. 14B shows a second state of the device of FIG. 14A after it has reached a desired position. [Figure 15] FIG. 15 illustrates a method for delivering a therapeutic formulation into the luminal wall of the GI tract or surrounding tissue of a subject via oral administration of an ingestible device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] Before describing the details of the ingestible devices, assemblies, and methods of the present disclosure, some conventions are provided for the convenience of the reader.

[0037] As used in this disclosure, the terms "eg," "such as," "for example," "for an example," "for another example," "example of," "by way of example," and "etc." indicate that a list of one or more non-limiting example(s) is preceded or followed, and it is to be understood that other unlisted examples are within the scope of the disclosure.

[0038] As used herein, the singular terms "a," "an," and "the" may include plural references unless the context clearly dictates otherwise. Additionally, the singular terms "a," "an," and "the" do not mean "one and only one" unless expressly stated otherwise, but rather "one or more."

[0039] As used herein, a phrase in the form "A / B" or in the form "A and / or B" means (A), (B), or (A and B), and a phrase in the form "at least one of A, B, or C" means (A), (B), (C), (A and B), (A and C), (B and C), or (A, B, and C).

[0040] The term "in one embodiment" or variations thereof (e.g., "in another embodiment" or "in one embodiment") is used herein to refer to use in one or more embodiments and does not in any way limit the scope of the disclosure to only the embodiments shown and / or described. Thus, components illustrated and / or described herein with respect to an embodiment can be omitted or used in another embodiment (e.g., another embodiment illustrated and described herein, or another embodiment within the scope of the disclosure but not illustrated and / or described herein).

[0041] As used herein, the term "component" refers to one item of a set of one or more items that collectively constitute the device, composition, or system under discussion. A component may be a solid, powder, gel, plasma, fluid, gas, or other configuration. For example, a device may include multiple solid components that are assembled together to constitute the device and may further include a fluid component disposed within the device. As another example, a composition may include a single component, or two or more components that are mixed together to make the composition. A composition may be in the form of a fluid, slurry, powder, or solid (e.g., in a compacted or combined form such as a tablet or microtablet). A device or system may include one or more compositions and / or one or more other components.

[0042] The term “design” or grammatical variations thereof (e.g., “designing” or “designed”), as used herein, refers to features that are intentionally built into a device based on, for example, estimates of tolerances (e.g., component tolerances and / or manufacturing tolerances) and estimates of the environmental conditions that are expected to be encountered (e.g., temperature, humidity, external or internal ambient pressure, external or internal mechanical pressure, stress due to external or internal mechanical pressure, or, if introduced into the body, physiology, body chemistry, biological composition). It is understood that different components, devices, compositions, or systems with identical designs may have different actual values ​​for these properties, since internal ambient pressure, external or internal mechanical pressure, stress from external or internal mechanical pressure, age or shelf life of the product, or if introduced into the body, physiology, body chemistry, biological composition of body fluids or tissues, chemical composition of body fluids or tissues, pH, species, diet, health, sex, age, ancestry, disease, or tissue damage), actual tolerances and environmental conditions before and / or after delivery may affect the properties. Design also includes pre- or post-manufacturing changes or modifications.

[0043] The term "structured" or grammatical variations thereof (e.g., "structure" or "structuring"), as used herein, refers to a component, device, composition, or system that is produced according to a concept or design, or variations or modifications thereof (whether such variations or modifications occur before, during, or after production), regardless of whether such concept or design is described in writing.

[0044] As used herein, the term "body" refers to an animal body, unless the context clearly indicates otherwise.

[0045] As used herein, the term "subject" refers to a body to which an embodiment of the present disclosure is delivered or is intended to be delivered. For example, with respect to a human, a subject may be a patient receiving treatment from a medical professional. The terms "individual," "subject," and "patient" may be used interchangeably herein and refer to any individual animalia, subject (e.g., cow, dog, cat, horse, or human). In certain embodiments, the subject, individual, or patient is a human.

[0046] The term "fluid" as used herein refers to a liquid or gas, and includes water and humidity. The term "fluidic environment" as used herein refers to an environment in which one or more fluids are present.

[0047] The term "ingest" or grammatical variations thereof (e.g., "ingesting," "ingestion," or "ingested"), as used herein, refers to taking into the stomach, whether by swallowing or by other means of deposition into the stomach (e.g., deposition into the stomach by an endoscope or via a port).

[0048] The term "degrade" or grammatical variations thereof (e.g., "degrading," "degraded," "degradable," and "degradation"), as used herein, refers to weakening, partial degradation, or complete breakdown, such as by dissolution, chemical degradation (including biodegradation), breakdown, chemical modification, mechanical degradation, or disintegration, including, but not limited to, dissolving, crumbling, deformation, withering, or shrinking. The term "non-degradable" means that in the expected environment, at least for the expected period of time, degradation is minimal or within some acceptable design rate.

[0049] The term "degradation rate" or grammatical variations thereof (e.g., "rate of degradation"), as used herein, refers to the rate at which a material breaks down. The designed degradation rate of a material in certain embodiments can be defined by the rate at which the material is expected to degrade under the conditions (e.g., physiological conditions) expected at the target delivery site. The designed degradation time for certain embodiments can refer to the designed time to complete degradation or the designed time to partial degradation sufficient to achieve the design objective (e.g., breach). Thus, for example, the designed degradation time can be component specific and / or specific to the conditions expected at the target delivery site. The designed degradation time can be short or long and can be defined in terms of an approximate time, a maximum time, or a minimum time.

[0050] As used herein, the term "substantially" is used to describe and take into account small variations that may result, for example, from manufacturing or assembly processes. For example, when used with a numerical value, the term can refer to a variation in the numerical value of ±10% or less.

[0051] As used herein, the term "lumen" refers to the interior space of a tubular structure. Examples of lumens in the body include arteries, veins, lumens within organs, etc.

[0052] The term "lumen wall" means the wall of a lumen, and includes all layers of the lumen from the inner periphery to the outer periphery. For example, with respect to a lumen in the body, it includes the mucosa, submucosa, muscularis, serosa, the outer wall of the lumen, and the blood vessels and tissues that constitute it.

[0053] As used herein, the term "gastrointestinal tract" or "GI tract" refers to the intake / excretion system of the body including, for example, the mouth, pharynx, esophagus, stomach, pylorus, small intestine, cecum, large intestine, colon, rectum, anus, and the valves or sphincters between them.

[0054] The term "GI lumen" generally refers to any lumen of the GI tract (eg, the lumen of the esophagus, stomach, small intestine, large intestine, colon), and the term "GI lumen wall" refers to the luminal wall of the GI lumen.

[0055] As used herein, the terms "comprising," "comprise," "comprises," "includes," and "including" are intended to mean that the compositions and methods include the recited elements, but do not exclude other elements.

[0056] As used herein, the phrase "therapeutically effective amount" of a drug refers to a dose of the drug that provides the specific pharmacological effect for which the drug is administered in a subject in need of such treatment. It is emphasized that a therapeutically effective amount of a drug, even if considered therapeutically effective by those skilled in the art, may not always be effective in treating a target condition in an individual subject. Those skilled in the art can adjust what is considered a therapeutically effective amount according to standard practices as necessary to treat a particular subject. A therapeutically effective amount can vary, for example, based on the age and weight of the subject, and / or the overall health of the subject, and / or the severity of the subject's condition being treated.

[0057] Referring generally to the Figures, disclosed herein are embodiments of ingestible devices, assemblies, and methods for delivering a therapeutic formulation to the luminal wall of the GI tract of a subject or surrounding tissues (e.g., the peritoneum or peritoneal cavity). The ingestible device is advantageously structured to temporarily protect the therapeutic formulation from degradation within at least a portion of the GI tract until delivery. Delivery to the luminal wall or surrounding tissues allows for systemic uptake of one or more therapeutic agents of the therapeutic formulation. Various types of therapeutic agents are described below, examples of which include macromolecules that are not typically suitable for delivery by ingestion. In this manner, the disclosed ingestible devices, assemblies, and methods address many of the shortcomings associated with conventional oral and parenteral routes of administration.

[0058] 1 illustrates, in block diagram form, an example of an ingestible device 100 in accordance with one or more embodiments of the present disclosure. Ingestible device 100 includes a housing 102, an optional outer coating 104, a release means 108, an actuator 110, a support 115, a delivery assembly 120, a therapeutic formulation 125, a delivery structure 128, and an expander 130. In one or more embodiments, support 115 can form a portion of at least one of delivery assembly 120, actuator 110, or expander 130.

[0059] According to non-limiting examples, the housing 102 (or optionally the housing 102 and / or the outer coating 104) can be degraded at a desired location within the subject's GI tract for delivery of the therapeutic formulation 125, as described in more detail below. In response to at least partial degradation of the housing 102 and / or the outer coating 104, the release means 108 can be actuated to actuate the actuator 110, as described in more detail below. The actuator 110 can then axially stretch at least one of the support 115 or the stretcher 130 to align the delivery structure 128 against the GI luminal wall of the subject. The actuator 110, substantially simultaneously or after actuating the stretcher 130, moves the delivery assembly 120 outwardly toward the GI luminal wall, delivering the therapeutic formulation 125 from the delivery structure 128 into the luminal wall or into the surrounding tissue, where one or more therapeutic agents of the therapeutic formulation 125 can be expelled into the subject's bloodstream for systemic uptake.

[0060] Enclosure 102 and / or outer coating 104 are configured to allow ingestion of ingestible device 100 and temporarily protect the contents of ingestible device 100 from degradation within one or more portions of the GI tract of a subject. Enclosure 102 can take a variety of different forms and shapes, such as a swallowable capsule (e.g., a size 00 capsule, a size 000 capsule, or other size capsule), or any other structure suitable for ingestion by a subject and capable of housing or containing one or more components of ingestible device 100. In one or more embodiments, housing 102 includes two or more segments that are joined (e.g., press-fit) together to define housing 102. For example, housing 102 may be configured as a capsule that includes a first segment that at least partially overlaps a second segment in a press-fit arrangement to define housing 102. The first and second segments may be removably coupled, for example, to allow separation of the two segments by application of an internal force (e.g., by stretching the support 115, the delivery assembly 120, and / or the stretcher 130). The release means 108, the actuator 110, the support 115, the delivery assembly 120, the therapeutic formulation 125, the delivery structure 128, and the stretcher 130 are each structured to be contained within the interior of the housing 102. The release means 108 may optionally be located outside the interior of the housing 102, such as on an exterior portion of the housing 102. In other embodiments, the outer coating 104 may itself function as a container or protective layer to contain / protect one or more of the release means 108, the actuator 110, the support 115, the delivery assembly 120, the therapeutic formulation 125, the delivery structure 128, and the stretcher 130 therein without going through the housing 102.

[0061] In one or more embodiments, the housing 102 (or optionally the housing 102 and / or the outer coating 104) can degrade under certain conditions. Additionally, different portions of the housing 102 can be structured to degrade under different conditions or at different degradation rates depending on the target site in the GI tract for delivery of the therapeutic formulation 125. For example, some or all of the housing 102 can be constructed of a material that degrades in water (e.g., in the presence of water in the form of humidity or moisture in an ambient environment such as within the body) and / or that degrades when exposed to a solution having a pH level above a certain threshold or within a certain range (e.g., a pH level associated with a desired location or portion of the GI tract). In other embodiments, the housing 102 degrades in response to a temperature threshold. In other embodiments, the housing 102 is substantially non-degradable or includes substantially non-degradable portions.

[0062] The outer coating 104 optionally covers part or all of the housing 102. In other embodiments, the outer coating 104 directly covers one or more of the release means 108, the actuator 110, the support 115, the delivery assembly 120, the therapeutic formulation 125, the delivery structure 128, and the stretcher 130 without the housing 102. In these embodiments, the outer coating 104 can function as a protective layer to temporarily protect one or more components of the ingestible device 100 from degradation in the GI tract without a separate housing 102. The outer coating 104 can include a single layer or multiple layers. The various layers can be formed of the same material or a combination of different materials. One example of an outer coating 104 is an enteric coating that degrades at a predetermined rate in water and / or when exposed to a solution having a pH level above a certain threshold or within a certain range. Another example of the outer coating 104 is a protective coating (eg, a wax), such as a coating that protects a portion of the outer surface of the housing 102 from contact with fluids or tissue (eg, body tissue or fluids).

[0063] In one or more embodiments, the dissolution of the housing 102 and / or the outer coating 104 can allow fluids (e.g., gastric or intestinal fluids) to enter the interior of the housing 102 / outer coating 104 and activate the release means 108. Alternatively, the release means 108 can be located on an outer portion of the housing 102, and the dissolution of the outer coating 104 can expose the release means 108 to a surface of the housing 102 to facilitate actuation of the release means 108. Alternatively, the release means 108 can be located on a portion of the housing 102 that is free of the outer coating 104, and the release means 108 can be structured to dissolve at a different rate than the housing 102 and / or under different conditions within the GI tract. The housing 102 and / or the outer coating 104 can define one or more dissolution regions for localized dissolution of the housing 102 and / or the outer coating 104, for example, to allow at least one of the support 115, the delivery assembly 120, or the stretcher 130 to apply a force within the housing 102 to force the housing 102 apart. For example, the outer coating 104 can be selectively applied only to certain regions of the housing 102 (e.g., ends of the housing 102) to expose selected portions of the housing 102 (e.g., a mid-portion of the housing 102 between the ends), thereby defining regions of the housing 102 that can degrade at a faster rate and / or degrade sooner than other regions of the housing 102. This controlled degradation of the housing 102 can allow for more consistent separation of the housing 102 (e.g., by forming a substantially unobstructed region between the separated portions of the housing 102 for deployment of the delivery structure 128) to thereby enable delivery of the therapeutic formulation 125 from the delivery structure 128 to the GI lumen wall.

[0064] The release means 108 is a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical-chemical structure. In one or more embodiments, the release means 108 is configured to be actuated (e.g., degrade, release, move, open) in response to conditions in the GI tract. For example, the release means 108 may be structured to degrade in water such that the release means 108 degrades when it comes into contact with liquid in the GI tract. As another example, the release means 108 may be configured to degrade above a particular pH level or within a range of pH levels associated with a location in the GI tract (e.g., stomach pH, ​​intestinal pH). In these and other embodiments, the release means 108 may be made from a biodegradable material, such as an enteric material. Additionally or alternatively, the release means 108 may be configured as a latch, clip, cover, plug, coating, or any other structure that moves, opens, or otherwise releases in response to conditions in the GI tract (e.g., pH). The release means 108 may be formed from a single material or a combination of materials. The release means 108 may include one or more components. In embodiments in which multiple components are included in the release means 108, the components may be co-located (e.g., coaxial) or may be physically separated from one another.

[0065] The release means 108 is coupled to the actuator 110 such that, upon actuation of the release means 108, the actuator 110 can axially extend the stretcher 130 and / or outwardly extend the delivery assembly 120 to deliver the therapeutic formulation 125 from the delivery structure 128 into the GI lumen wall. In one or more embodiments, the release means 108 is disposed within the interior of the housing 102 / outer coating 104. In other embodiments, the release means 108 is disposed on a portion (e.g., an exterior surface) of the housing 102.

[0066] Ingestible device 100 may include multiple release means (e.g., release means 108 and / or other release mechanisms) that operate under different conditions and / or at different rates to cause sequential actuation of various components of ingestible device 100. In one or more embodiments, ingestible device 100 may be structured to selectively expose and / or activate one or more additional release mechanisms in response to movement of a component of ingestible device 100 following actuation of release means 108. For example, ingestible device 100 may include a first release means (e.g., release means 108) associated with actuator 110 and a second release means (e.g., release mechanism) associated with a component of delivery assembly 120, such as an actuation mechanism of delivery structure 128. In this example, the first release means can be configured to actuate earlier and / or at a faster rate than the second release means, such that actuation of the first release means can cause the actuator 110 to move one or more components of the delivery assembly 120 to a desired position relative to the GI luminal wall prior to actuation of the second release means. Additionally or alternatively, movement of the delivery assembly 120 (e.g., pivotable movement of one or more arms) can expose or move the second release means to actuate the second release means. Actuation of the second release means can then cause the delivery structure 128 to actively deliver the therapeutic formulation 125 to the GI luminal wall when the delivery assembly 120 is positioned proximate to the GI luminal wall.

[0067] According to another embodiment, a first release means can be associated with a first actuator and a second release means can be associated with a second actuator. The first actuator can be coupled to the stretcher 130 and the second actuator can be coupled to the delivery assembly 120, and actuation of the first release means can stretch the stretcher 130 prior to actuation of the second release means to align the delivery structure 128 relative to the GI lumen wall. Actuation of the second release means can then cause the second actuator to move one or more components of the delivery assembly 120 relative to the GI lumen wall to deliver the therapeutic formulation 125 from the delivery structure 128 into the GI lumen wall.

[0068] The actuator 110 is a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical-chemical structure. In one or more embodiments, the actuator 110 is a structure that actuates at least one of the stretcher 130, the delivery assembly 120, or the support 115 in response to actuation of the release means 108. The actuator 110 may be a structure that axially stretches the stretcher 130 to align the delivery structure 128 relative to the GI luminal wall. Additionally or alternatively, the actuator 110 may be a structure that pivots one or more components of the delivery assembly 120 to move the delivery structure 128 proximate to the GI luminal wall to deliver the therapeutic formulation 125 from the delivery structure 128 into the luminal wall. Additionally or alternatively, the actuator 110 may be a structure that axially stretches, adjusts, and / or moves the support 115 along a longitudinal axis defined by the support 115. Actuator 110 may be a structure that causes substantially simultaneous actuation of any combination of support 115, delivery assembly 120, or stretcher 130. Actuator 110 may include one or more components. In embodiments in which multiple components are included in actuator 110, the components may be co-located or physically separated from one another. In one or more embodiments, ingestible device 100 may include multiple actuators (e.g., including actuator 110) or actuation mechanisms. For example, ingestible device 100 may include a separate actuator associated with any one of stretcher 130, delivery assembly 120, and delivery structure 128, or a combination thereof.

[0069] The support 115 is a mechanical structure for holding and providing structural support to at least one of the actuator 110, the delivery assembly 120, the therapeutic formulation 125, the delivery structure 128, or the stretcher 130 within the housing 102. In one or more embodiments, the support 115 can form a portion of at least one of the actuator 110, the delivery assembly 120, or the stretcher 130. The support 115 is a generally elongated member and may include one or more sections that define a longitudinal axis of the ingestible device 100. In embodiments that include one or more sections, the sections may be movably (e.g., slidably) coupled, for example, such that the support 115 defines an axially extendable (e.g., telescopic) arrangement in response to actuation of the actuator 110. The support 115 may be movable relative to other components of the ingestible device 100, for example, to cause actuation of the delivery assembly 120 and / or the stretcher 130. The support 115 may include one or more components. In embodiments in which multiple components are included on support 115, the components may be co-located (eg, coaxial) or may be physically separated from one another.

[0070] The delivery assembly 120 is a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical structure. In one or more embodiments, the delivery assembly 120 is coupled to the support 115 via one or more arms pivotally coupled to the support 115. The arms may form part of the device 100 and / or the delivery assembly 120. The delivery assembly 120 further includes a delivery structure 128 for housing the therapeutic formulation 125 and delivering the therapeutic formulation 125 into the GI lumen wall. One or more components of the delivery assembly 120 are configured to pivot relative to the support 115 in response to actuation of the actuator 110 to cause the delivery assembly 120 to extend outwardly from the support 115 toward the GI lumen wall via the one or more arms for delivery of the therapeutic formulation 125. For example, in one or more embodiments, the device 100 includes multiple arms pivotally coupled together in a cross shape to define a scissor mechanism. In other embodiments, device 100 includes a single pivotable arm pivotally coupled to support 115. The pivotable arm is configured to pivot away from support 115 about a single pivot axis on support 115. One or more components of delivery assembly 120 may be movably coupled to support 115 to enable translational movement of delivery assembly 120 relative to support 115. Ingestible device 100 may include one or more delivery assemblies 120. Delivery assembly 120 may include one or more components. In embodiments in which multiple components are included in delivery assembly 120, the components may be co-located or physically separated from one another.

[0071] Therapeutic formulation 125 is a formulation that includes one or more components where the formulation is intended for a therapeutic, diagnostic, or other biological purpose. Therapeutic formulation 125 may be in liquid form, powder form, or in a compacted or combined form such as a tablet or micro-tablet. The components of therapeutic formulation 125 may be, for example, a therapeutic agent such as a pharmacologically active agent (e.g., a drug, protein, peptide, etc., a drug, protein, peptide, polypeptide, antibody, oligonucleotide), a DNA or siRNA transcript, a cell, a cytotoxic agent, a vaccine or other prophylactic agent, a nutritional supplement, a vasodilator or vasoconstrictor, a delivery enhancer, a retardant, an excipient, a diagnostic agent, or a substance for cosmetic enhancement. Therapeutic formulation 125 may include a therapeutically effective amount of a therapeutic agent or other components in an appropriate amount to achieve a desired therapeutic effect in a subject. Ingestible device 100 may include one or more therapeutic formulations 125 disposed in each delivery assembly 120 for delivery to the GI lumen wall. In embodiments including one or more therapeutic formulations 125, each therapeutic formulation 125 may include the same ingredients or different ingredients (e.g., different pharmacologically active agents) to provide a particular therapeutic effect.

[0072] In one or more embodiments, the therapeutic formulation 125 includes a structure for inserting the therapeutic formulation 125 into the GI lumen wall. For example, the therapeutic formulation 125 may include a biodegradable structure defining a cavity for containing one or more components of the therapeutic formulation 125 therein. The biodegradable structure may further include a tapered end (e.g., a spike, lance, or otherwise pointed end) for puncturing and inserting the therapeutic formulation 125 into the GI lumen wall or into the surrounding tissue. Additionally or alternatively, the therapeutic formulation 125 may be deposited (e.g., dipped, sprayed) as a coating on a surface of the biodegradable structure. The biodegradable structure may degrade within the tissue of the GI lumen wall or within the tissue surrounding the GI lumen wall to expel the therapeutic agent of the therapeutic formulation 125 from the biodegradable structure into the bloodstream of the subject. For example, the biodegradable structure may be composed of a biodegradable polymer (e.g., polyethylene glycol (PEG)), cellulose, and / or a sugar such as maltose. In other embodiments, the therapeutic formulation 125 can itself be formed into a shaped structure with a tapered end for penetrating the GI lumen wall without a separate biodegradable structure. In these embodiments, the therapeutic formulation 125 is a rigid or semi-rigid structure with a defined shape and sufficient rigidity to puncture and insert into the GI lumen wall or surrounding tissue where one or more therapeutic agents of the therapeutic formulation 125 can be expelled into the subject's bloodstream. It should be understood that the ingestible device 100 may include any one or combination of the various forms of the therapeutic formulation 125 described above.

[0073] The therapeutic formulation 125 is contained within a sealed container to substantially preserve the therapeutic formulation 125 for delivery within the GI lumen wall to achieve a desired therapeutic effect in a subject. In one or more embodiments, the sealed container may include a body defining an interior for containing the therapeutic formulation 125 therein, and one or more degradable seals (e.g., foil, film) coupled to the body to substantially seal the interior to temporarily protect the therapeutic formulation 125 from degradation within the GI lumen prior to delivery within the lumen wall. The sealed container forms part of the delivery structure 128 of the delivery assembly 120. The therapeutic formulation 125 is configured to pierce and penetrate the degradable seal of the sealed container for delivery from the delivery structure 128 into the GI lumen wall.

[0074] The delivery structure 128 is a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical-chemical structure. The delivery structure 128 forms part of the delivery assembly 120. The delivery structure 128 is a structure that holds a sealed container containing the therapeutic formulation 125. In one or more embodiments, the delivery structure 128 may be a structure that delivers the therapeutic formulation 125 from the sealed container to the GI luminal wall. For example, the delivery structure 128 may include a holder having a protrusion. The sealed container may be movably (e.g., slidably) coupled to the holder adjacent the protrusion such that when the delivery assembly 120 is actuated, the sealed container is pushed back against the protrusion by the luminal wall to puncture a degradable seal of the container, and the protrusion contacts the GI luminal wall with sufficient force to cause the therapeutic formulation 125 to be expelled from the container to the GI luminal wall. In other words, the delivery structure 128 delivers the therapeutic formulation 125 without a separate release / actuation mechanism because it relies on a return force from contact with the GI luminal wall.

[0075] Additionally or alternatively, the delivery structure 128 may be structured to deliver the therapeutic formulation 125 from the sealed container to the GI lumen wall using a separate actuation mechanism. For example, the delivery structure 128 may include a separate actuation mechanism (e.g., a spring, a piston, an igniter / charge, a gas) and a corresponding release mechanism for triggering the actuation mechanism to actively apply a force to the surface of the therapeutic formulation 125 such that the therapeutic formulation 125 is expelled from the container to the GI lumen wall. The release mechanism may be structured to act in sequence with the release means 108. For example, the release mechanism may be structured to be actuated in response to movement of the delivery assembly 120 (e.g., by selectively exposing the release mechanism to gastrointestinal fluids). Additionally or alternatively, the release mechanism may have a different degradation rate than the release means 108 to cause actuation of the release mechanism after the delivery assembly 120 is actuated. In one or more embodiments, the delivery structure 128 may further include retention features (e.g., hooks, barbs) for temporarily retaining the delivery structure 128 against the GI lumen wall to facilitate delivery of the therapeutic formulation 125 to the GI lumen wall.

[0076] It should be appreciated that the ingestible device 100 may include any one or combination of a variety of delivery structures 128 for delivering the therapeutic formulation 125 into the GI lumen wall.

[0077] The stretcher 130 is a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical-chemical structure. The stretcher 130 is an adjustable structure. In one or more embodiments, the stretcher 130 is coupled to the support 115 and configured to stretch (e.g., expand, stretch, inflate) at least axially along a longitudinal axis defined by the support 115 to aid in alignment of the delivery assembly 120 relative to the GI lumen wall. For example, the stretcher 130 can stretch axially along a longitudinal axis defined by the support 115 such that the longitudinal axis is substantially aligned with the longitudinal axis of the subject's GI lumen, thereby allowing the delivery structure 128 to be oriented substantially orthogonally relative to the GI lumen wall upon actuation of the actuator 110. The substantially orthogonal orientation of the delivery structure 128 relative to the GI lumen wall can help promote sufficient penetration of the therapeutic formulation 125 into the lumen wall tissue. The stretcher 130 may stretch in response to actuation of the actuator 110 or in response to a separate actuator. The stretcher 130 may include one or more components. In embodiments in which multiple components are included in the stretcher 130, the components may be co-located or physically separated from one another.

[0078] One or more components of the ingestible device 100 (e.g., capsule 102, release means 108, actuator 110, support 115, delivery assembly 120, delivery structure 128, expander 130) may be formed from or otherwise include one or more biodegradable materials to facilitate degradation of such components, e.g., to allow passage through the remainder of the subject's intestinal tract following delivery of the therapeutic formulation 125. Examples of biodegradable materials that may be suitable for use with various components of the ingestible device 100 include, for example, hydroxypropyl methylcellulose (HPMC), polyvinyl acetate (PVA), lactide, glycolide, lactic acid, glycolic acid, per-dioxanone, trimethylene carbonate, caprolactone, and mixtures and copolymers thereof.

[0079] The above description is an overview of ingestible device 100. The following description, with reference to Figures 2A-15, relates to examples of various features and aspects of ingestible device 100 for delivering therapeutic formulation 125 into the GI lumen wall. These examples are illustrative of ingestible device 100, but are not intended to be limiting of ingestible device 100.

[0080] 2A, a side cross-sectional view of an ingestible device 100' in capsule form is illustrated in a first state prior to the ingestible device 100' reaching a desired location in the GI tract to deliver a therapeutic formulation 125. Although the ingestible device 100' is illustrated without any components disposed therein, it should be understood that the ingestible device 100' may include at least one of a release means 108, an actuator 110, a support 115, a delivery assembly 120, a therapeutic formulation 125, a delivery structure 128, or a stretcher 130 disposed therein. As shown in FIG. 2A, the ingestible device 100' includes a housing 102' (one embodiment of the housing 102) configured as a swallowable capsule having a generally cylindrical body and a hemispherical end defined by a first segment 102a' and a second segment 102b'. The first segment 102a' is removably coupled to the second segment 102b' in an arrangement in which the first segment 102a' overlaps the second segment 102b'. The first segment 102a' may be press-fit into the second segment 102b'. The first segment 102a' and the second segment 102b' may be sealed together along an outer seam between the two segments 102a' and 102b'. The first segment 102a' and the second segment 102b' cooperate to define an interior 102c' for housing therein one or more of the release means 108, the actuator 110, the delivery assembly 120, the therapeutic compound 125, the delivery structure 128, and the stretcher 130. Housing 102' includes an optional release means 108' (one embodiment of release means 108) extending through a portion of first segment 102a', which can be structured to cause actuation of an actuator (e.g., actuator 110) disposed within housing 102'. Ingestible device 100' further includes an outer coating 104' disposed on an exterior surface of housing 102' that temporarily protects release means 108' and housing 102' from degradation throughout one or more portions of the GI tract.

[0081] 2B, the ingestible device 100' is shown in a second state in which the ingestible device 100' has reached a desired location in the GI tract to trigger degradation of the outer coating 104' and / or the housing 102'. For example, one or more portions of the outer coating 104' and / or one or more portions of the housing 102' can be structured to degrade at a threshold pH value, or within a range of pH values, associated with a desired location in the stomach or intestine (e.g., small intestine) to deliver the therapeutic compound 125 into the luminal wall of the subject. The release means 108' can be structured to degrade under the same or different conditions as the outer coating 104' and / or the housing 102' to trigger alignment of the delivery structure 128 for delivery of the therapeutic compound 125. For example, degradation of the release means 108' can cause actuation of the actuator 110, thereby stretching at least one of the stretcher 130 or the delivery assembly 120. In response, at least one of the support 115, the delivery assembly 120, or the stretcher 130 can cause or assist in axial separation of the first segment 102a' from the second segment 102b', as generally represented by block arrows in Figure 2B. Separation of the first segment 102a' from the second segment 102b' can advantageously help to facilitate alignment of the delivery structure 128 (as discussed above) and actuation of the delivery assembly 120 (e.g., by forming a substantially unobstructed area for deployment of the delivery structure 128) to facilitate delivery of the therapeutic formulation 125 to the GI lumen wall.

[0082] 3A, a side cross-sectional view of an ingestible device 200 including an actuator in the form of a spring 210 (one embodiment of actuator 110) is shown. Ingestible device 200 is illustrated in a first state before ingestible device 200 reaches a desired location within the GI lumen for delivery of therapeutic formulation 125 into the GI lumen wall. Ingestible device 200 includes a housing 202 (an embodiment of housing 102) and an outer coating 204 (an embodiment of outer coating 104). Housing 202 is configured as a capsule having a first segment 202a removably coupled to a second segment 202b.

[0083] Ingestible device 200 further includes a support 215 (one embodiment of support 115) disposed within housing 202. Support 215 defines a general longitudinal axis 201 of ingestible device 200. Support 215 includes a first support 214 and a second support 216. First support 214 is movably coupled to second support 216 so as to be disposed generally telescopically. In the illustrated example, first support 214 is disposed partially on and slidably coupled to second support 216. First support 214 and second support 216 have complementary shapes or include complementary portions to each other to enable relative translational (e.g., sliding) movement. First support 214 defines first support first end 214a and first support second end 214b. Similarly, the second support 216 defines a second support first end 216a and a second support second end 216b. The first support 214 further includes a protrusion 214c disposed on an outer surface thereof. The protrusion 214c defines an engagement surface for engaging the spring 210 upon expansion of the spring 210, as will be described in more detail in a subsequent paragraph.

[0084] Referring again to FIG. 3A, the spring 210 is disposed on an outer portion of the first support 214. Although the spring 210 is shown as a coil spring, it should be understood that the spring 210 may be any type of spring (e.g., helical), or any other type of biasing member that can function similarly to a spring. In the position shown in FIG. 3A, the spring 210 is held in a compressed state by a release means 208 (an embodiment of the release means 108) coupled to the spring 210. For example, the release means 208 can surround at least a portion, or all, of the spring 210 to hold one or more coils of the spring 210 in a compressed state. The ingestible device 200 further includes a slidable member 217 slidably coupled to the second support 216. The slidable member 217 may be a hub, a sleeve, a piston, a protrusion, a gear, or any other feature that can be movably coupled to the second support 216. For example, the second support 216 may include a slot, channel, exterior surface, or other complementary feature that movably receives the slidable member 217. In a first state, shown in FIG. 3A, the slidable member 217 is disposed adjacent the first support second end 214b. At least a portion of the second support 216 is configured to permit slidable movement of the slidable member 217 relative to the second support 216. The slidable member 217 and the second support 216 may be constructed of one or more materials having a sufficiently low coefficient of friction to permit relative sliding movement.

[0085] At least one of the first support 214 or the second support 216 can include a stop feature to limit the amount of relative axial movement between the two sections and prevent them from completely separating from one another.

[0086] The ingestible device 200 further includes a delivery assembly 220 (an embodiment of the delivery assembly 120) pivotally coupled to the support 215. In the embodiment shown in FIG. 3A, the ingestible device 200 includes two delivery assemblies 220 disposed on opposite sides of the support 215, however, it should be understood that the ingestible device 200 may include one or more, two or more, three or more, or four or more delivery assemblies 220 according to other embodiments. The device 200 pivotally couples the multiple arms 222a-d in a cross shape to define multiple crosses 220a, 220b of a scissor mechanism (similar to a scissor lift) configured to extend outwardly away from the longitudinal axis 201 toward the GI luminal wall of the subject to deliver the therapeutic formulation 125 into the luminal wall, as described below. Although arms 222a-d are shown as substantially linear members, arms 222a-d may be substantially non-linear or may include substantially non-linear portions according to other embodiments.

[0087] As shown in FIG. 3A, the device 200 includes two pivotally coupled crosses 220a, 220b. The first cross 220a includes a first arm 222a pivotally coupled to the second support 216 at or near the second support first end 216a by a first pivot joint 224a. The first cross 220a further includes a second arm 222b pivotally coupled to the slidable member 217 by a second pivot joint 224b. The first arm 222a and the second arm 222b are arranged in a cross shape relative to one another and pivotally coupled by a third pivot joint 224c at a location between the ends of each arm 222a, 222b to define the first cross 220a. The second cross section 220b is pivotally coupled to the first cross section 220a at or near a distal end of the first cross section 220a. For example, the second cross section 220b includes a third arm 222c pivotally coupled to an end of the first arm 222a by a fourth pivot joint 224d. The second cross section 220b further includes a fourth arm 222d pivotally coupled to an end of the second arm 222b by a fifth pivot joint 224e. The third arm 222c and the fourth arm 222d are arranged in a cross shape relative to one another and pivotally coupled by a sixth pivot joint 224f at a location between the ends of the arms 222c, 222d to define the second cross section 220b. Each of pivot joints 224a-224f may be configured as a pin, ball-and-socket joint, hinge, or other joint (passive or active) that can enable relative pivotable movement between respective arms 222a-222d. As discussed above, device 200 can include any number of cross sections (e.g., cross sections 220a, 220b, and additional or fewer cross sections similar to or instead of cross sections 220a, 220b).

[0088] The delivery assembly 220 further includes a platform 226 pivotally and slidably coupled to the second cross 220b at or near a distal end of the second cross 220b by seventh and eighth pivot joints 224g, 224h, respectively. For example, the pivot joints 224g, 224h may each be configured as a pin, ball and socket joint, hinge, or other joint, and the platform 226 may include one or more rails, channels, slots, or other complementary features for engaging the pivot joints 224g, 224h to enable slidable and pivotable movement of the second cross 220b relative to the platform 226. The platform 226 is generally planar and is a structure that provides support for a delivery structure 128 that is coupled to or formed integrally with the platform 226. The delivery structure 128 and therapeutic compound 125 are shown in block diagram form in Figures 3A-3B, with the delivery structure 128 being a structure that contains one or more therapeutic compounds 125 therein and expels the therapeutic compounds 125 from the delivery structure 128 into the lumen wall or surrounding tissue. Various embodiments of the delivery structure 128 are described in more detail below with reference to Figures 10A-13B.

[0089] As described below with reference to FIG. 3B, the arms 222a-d are configured to pivot relative to one another and to the platform 226 to adjust each delivery assembly 220 from a collapsed state (shown in FIG. 3A) to an extended state (shown in FIG. 3B) to facilitate delivery of the therapeutic formulation 125 from the delivery structure 128 into the GI lumen wall. Each delivery assembly 220 may be configured to extend outwardly until the delivery structure 128 contacts the GI lumen wall. Additionally or alternatively, the delivery assemblies 220 may be configured to extend outwardly from the support 215 within a particular distance, or range of distances, for example, by selecting the size (e.g., length) of the arms 222a-d, selecting the number of cruciforms to include in each delivery assembly 220, and / or selecting the springs 210 (e.g., spring stiffness, spring travel).

[0090] Referring again to FIG. 3A, the ingestible device 200 further includes a stretcher 230 (an embodiment of the stretcher 130) coupled to the support 215 and the slidable member 217. The stretcher 230 is configured to extend axially along the longitudinal axis 201 to orient the ingestible device 200 within the GI lumen of the subject and facilitate delivery of the therapeutic formulation 125 in a manner generally perpendicular to the GI lumen wall. For example, the stretcher 230 includes a plurality of frame members 232a-h pivotally coupled together in a zigzag pattern by respective pivot joints 234a-i to define an expandable wire frame or skeleton-like structure. The pivot joints 234a-i can be of a similar structure to the pivot joints 224a-f described above. The stretcher 230 can include any number of frame members. The stretcher 230 can define a generally elongated structure having any suitable cross-sectional shape (e.g., circular, triangular, pentagonal, hexagonal). Additionally or alternatively, the stretcher 230 can be a hollow unitary structure including one or more concentric sides that can expand (similar to a bellows or accordion). The stretcher 230 defines a stretcher first end 230a and a stretcher second end 230b. The stretcher first end 230a is coupled to the first support 214 at or near the first support first end 214a. The stretcher second end 230b is coupled to the slidable member 217 (e.g., via a second pivot joint 224b). Although the expander 230 is shown disposed above the release means 208 and actuator 210, it should be understood that the release means 208 may be accessible through one or more openings in the expander 230 to allow for actuation of the release means 208 (e.g., disintegration due to contact with fluid in the GI tract).

[0091] 3B, the ingestible device 200 is shown in a second state after reaching a desired location within the GI lumen of the subject for delivery of the therapeutic formulation 125 from the delivery structure 128 to the GI lumen wall of the subject. As shown in FIG. 3B, the housing 202 and / or the outer coating 204 are partially (and may be completely) degraded as a result of the ingestible device 200 reaching a desired location within the GI tract, which is associated, for example, with a selected or threshold pH value for triggering the degradation of the housing 202 and / or the outer coating 204. As a result, fluid within the GI tract is permitted to reach the interior of the housing 202 to contact the release means 208 to actuate (e.g., degrade) the release means 208. In response to the actuation of the release means 208, the spring 210 is released from a compressed state (shown in FIG. 3A) to an expanded state (shown in FIG. 3B). Expansion of the spring 210 along the longitudinal axis 201 causes the first support 214 and the second support 216 to move axially away from each other, thereby extending the axial length of the support 215. Additionally, expansion of the spring 210 causes the slidable member 217 to translate (e.g., slide) axially along the second support 216 toward the second support first end 216a. For example, upon expansion of the spring 210, one end of the spring 210 contacts the protrusion 214c on the first support 214, urging the first support 214 axially away from the second support 216. A second, opposite end of the spring 210 contacts the slidable member 217, urging the slidable member 217 along the second support 216 toward the second support first end 216a.

[0092] Axial movement of the slidable member 217 toward the second support first end 216a and axial movement of the first support 214 away from the second support 216 also causes the stretcher 230 to extend axially along the longitudinal axis 201. For example, the stretcher first end 230a is in an axially fixed position relative to the first support 214. The stretcher second end 230b is coupled to the slidable member 217. Thus, translational movement of the slidable member 217 toward the second support first end 216a and axial movement of the first support 214 away from the second support 216 causes the stretcher 230 to extend axially in two directions along the longitudinal axis 201. 3B, axial movement of the first support 214 and / or the stretcher 230 can advantageously help to spread apart the first and second segments 202a, 202b of the capsule 202, thereby creating a substantially unobstructed area for deployment of the delivery structure 128 towards the GI lumen wall. Additionally, stretching of the stretcher 230 and stretching of the support 215 can help to substantially align the longitudinal axis 201 with the longitudinal axis of the GI lumen at the particular location within the lumen where the stretcher 230 and support 215 are actuated. Substantially aligning the longitudinal axis 201 with the longitudinal axis of the GI lumen can advantageously help to orient the delivery structure 128 substantially perpendicular to the GI lumen wall to help facilitate delivery of the therapeutic formulation 125 to the GI lumen wall.

[0093] Axial movement of slidable member 217 along longitudinal axis 201 also causes arms 222a-d to pivot relative to one another such that each delivery assembly 220 extends outwardly away from longitudinal axis 201 toward the GI lumen wall. For example, as shown in FIG. 3B, translation of second arm 222b toward first arm 222a via slidable member 217 causes second arm 222b to pivot about second pivot joint 224b and first arm 222a to pivot about first pivot joint 224a, as first arm 222a is in a fixed axial position relative to support 215. This movement causes the third arm 222c and the fourth arm 222d to pivot relative to each other and pivot / translate relative to the platform 226, thereby extending each delivery assembly 220 outward (e.g., laterally) away from the longitudinal axis 201. The outward extension of each delivery assembly 220 positions each delivery structure 128 adjacent to (or in engagement with) the GI lumen wall for delivery of the therapeutic formulation 125 (see, e.g., FIGS. 10A-13B and related discussion). After delivery of the therapeutic formulation 125 from the delivery structure 128, the remainder of the ingestible device 200 (e.g., the delivery assembly 220, the spring 210, the support 215, the delivery structure 128, and the extender 230) can disintegrate and / or pass through the remainder of the GI tract and out the subject's anus.

[0094] As can be seen from the above description, actuation of the single release means 208 causes the actuator 210 to substantially simultaneously stretch the support 215 and the stretcher 230 axially along the longitudinal axis 201 (as indicated by double arrow 236) and stretch each delivery assembly 220 outwardly from the longitudinal axis 201 (as indicated by single arrow 238). Relying on a single release means and actuator allows for consistent actuation of the support 215, the delivery assembly 220, and the stretcher 230, helping to achieve consistent alignment and deployment of the delivery structure 128 for delivery of the therapeutic formulation 125. Furthermore, the use of a single release means reduces the number of components of the ingestible device 200, thereby reducing the assembly time and cost of the device. According to other embodiments, it may be advantageous to include multiple release means (in addition to the release means 208) in the device 200, for example to sequentially actuate the support 215, the delivery assembly 220, and the stretcher 230.

[0095] For ease of reference, certain components above (or below) the support 215 are indicated with reference numerals in FIGS. 3A-3B, but no reference numerals are indicated for similar components above (or below) the support 215 (e.g., callouts are shown for arms 222a-d, pivot joints 224a-h, platform 226, extender 230 and its ends 230a, 230b, frame members 232a-h, pivot joints 234a-i), but it should be understood that similar components located above and below the support 215 are referenced by similar callouts.

[0096] 4A, a side cross-sectional view of an ingestible device 300 including an actuator in the form of an expandable member 310 (an embodiment of actuator 110) is shown. As described in more detail below, the expandable member 310 also functions as a stretcher 330 (an embodiment of stretcher 130) for the device. The ingestible device 300 is shown in a first state before the ingestible device 300 reaches a desired location within the GI lumen for delivery of the therapeutic formulation 125 into the GI lumen wall or surrounding tissue. The ingestible device 300 includes a housing 302 (an embodiment of housing 102) and an outer coating 304 (an embodiment of outer coating 104). The housing 302 is configured as a capsule having a first segment 302a removably coupled to a second segment 302b.

[0097] Ingestible device 300 further includes a support 315 (one embodiment of support 115) disposed within housing 302. Support 315 defines a general longitudinal axis 301 of ingestible device 300. Support 315 includes a first support 314 and a second support 316. First support 314 is movably coupled to second support 316 and disposed generally telescopically. In the illustrated example, first support 314 is disposed partially within and slidably coupled to second support 316. First support 314 and second support 316 have complementary shapes or include complementary portions to each other to enable relative translational (e.g., sliding) movement. First support 314 defines first support first end 314a and first support second end 314b. Similarly, second support 316 defines second support first end 316a and second support second end 316b. First support 314 includes a channel 314c extending from an outer side portion of first support 314 to first support first end 314a. Release means 318 is coupled to first support first end 314a to temporarily block channel 314c. Channel 314c and release means 318 collectively define a deflation valve for deflating expandable member 310, as described in further detail below.

[0098] Referring again to FIG. 4A, the expandable member 310 is coupled at a first end to the first support 314 and at a second end opposite the first end to the slidable member 317. The slidable member 317 is movably coupled to the second support 316 and is structured to translate (e.g., slide) axially relative to the second support 316 along the longitudinal axis 301. Although the expandable member 310 is shown as an inflatable balloon, the expandable member 310 may be a different structure, such as another type of inflatable structure having one or more concentric sides that are inflatable similar to an accordion or bellows. The expandable member 310 substantially surrounds at least a portion or all of the support 315. At least a portion of the expandable member 310 may be folded or otherwise positioned in the first state shown in FIG. 4A prior to expansion to improve the fit of the expandable member 310 within the housing 302.

[0099] The ingestible device 300 further includes a release means 308 (an embodiment of the release means 108) coupled to the expandable member 310. The release means 308 is coupled to the expandable member 310 to temporarily define a first chamber 310a and a second chamber 310b of the expandable member 310. The first chamber 310a is temporarily separated from the second chamber 310b and substantially sealed. For example, the release means 308 may be a band, clip, or other structure disposed on an outer portion of the expandable member 310 that pinches, folds, or compresses a portion (e.g., opposing sides) of the expandable member 310 to temporarily define separate first and second chambers 310a, 310b. The first chamber 310a includes a first reactant contained therein, such as an acid (e.g., citric acid). The second chamber 310b includes a second reactant contained therein, such as a carbonate (e.g., potassium bicarbonate). The expandable member 310 is composed of one or more layers of a flexible material (e.g., HPMC) that allows for expansion of the expandable member 310 in response to a chemical reaction caused by mixing of a first reactant and a second reactant within the expandable member 310. The expandable member 310 further includes an opening 310c in fluid communication with the channel 314c and functions as a portion of a deflation valve for deflating the expandable member 310.

[0100] Referring again to FIG. 4A, the ingestible device 300 further includes a delivery assembly 320 (an embodiment of the delivery assembly 120) pivotally coupled to the support 315. In the embodiment shown in FIG. 4A, the ingestible device 300 includes two delivery assemblies 320 disposed on opposite sides of the support 315, however, it should be understood that the ingestible device 300 may include one or more, two or more, three or more, or four or more delivery assemblies 320 according to other embodiments. The delivery assembly 320 is of similar structure to the delivery assembly 220 of FIGS. 3A-3B. Thus, for the sake of brevity, reference is made to the description of the delivery assembly 220 with respect to FIGS. 3A-3B for additional details regarding the structure and function of the delivery assembly 320.

[0101] As shown in FIG. 4A, the multiple arms 322a-322d pivotally couple each delivery assembly 320 to the support 315 in a cross shape by pivot joints 324a-324f, defining first and second cross portions 320a, 320b of a scissor mechanism (similar to a scissor lift) as discussed above with reference to the delivery assembly 220 of FIGS. 3A-3B, which are configured to extend outwardly from the longitudinal axis 301 toward the GI lumen wall of the subject to deliver the therapeutic formulation 125 into the GI lumen wall, as discussed above with reference to the delivery assembly 220 of FIGS. 3A-3B. The device 300 can include more or less than two cross portions according to other embodiments. The first arm 322a is pivotally coupled to the second support 316 at or near the first end 316a of the second support 316. The second arm 322b is pivotally coupled to the slidable member 317. The device 300 further includes a platform 326 that is pivotally and slidably coupled to the second cross 320b by pivot joints 324g-h. Coupled to or integrally formed with the platform 326 is a delivery structure 128 that includes one or more therapeutic compounds 125 therein.

[0102] 4B, the ingestible device 300 is shown in a second state in which the ingestible device 300 has reached a desired location within the GI lumen of a subject for delivery of the therapeutic formulation 125 from the delivery structure 128 to the GI lumen wall. As shown in FIG. 4B, the housing 302 and / or the outer coating 304 are partially (or completely) degraded as a result of the ingestible device 300 reaching a desired location within the GI tract, which is associated, for example, with a selected or threshold pH value for triggering the degradation of the housing 302 and / or the outer coating 304. As a result of the at least partial degradation of the housing 302 and / or the outer coating 304, fluid within the GI tract is permitted to reach the interior of the housing 302 to contact the release means 308 to activate (e.g., degrade) the release means 308. Actuation of the release means 308 places the first and second chambers 310a, 310b in fluid communication, which causes the first reactant to mix with the second reactant and undergo a chemical reaction to form a gas 319 (e.g., carbon dioxide gas (CO2)) and expand the expandable member 310 axially outwardly away from the longitudinal axis 301. Expansion of the expandable member 310 along the longitudinal axis 301 causes the first support 314 to move axially away from the second support 316, thereby extending the axial length of the support 315 (as indicated by double arrow 332). Additionally, expansion of the expandable member 310 causes the slidable member 317 to translate (e.g., slide) axially along the second support 316 toward the second support first end 316a. For example, upon expansion of the expandable member 310, the first end of the expandable member 310 axially moves the first support 314 away from the second support 316. The second of the expandable member 310 axially translates the slidable member 317 along the second support 316 toward the second support first end 316a.

[0103] As shown in FIG. 4B , the axial and / or outward expansion of the expandable member 310 can advantageously help to spread apart the first and second segments 302a, 302b of the capsule 302, thereby helping to create a substantially unobstructed area for the deployment of the delivery structure 128 towards the GI lumen wall. Additionally, the expansion of the expandable member 310 and the corresponding axial expansion of the support 315 can help to substantially align the longitudinal axis 301 with the longitudinal axis of the GI lumen at a location within the GI lumen where the expandable member 310 and the support 315 are actuated. In this manner, the expandable member 310 can effectively function as a stretcher 330 (an embodiment of the stretcher 130) of the ingestible device 300. Additionally, substantially aligning the longitudinal axis 301 with the longitudinal axis of the GI lumen can advantageously help to orient the delivery structure 128 substantially perpendicular to the GI lumen wall to facilitate delivery of the therapeutic formulation 125 from the delivery structure 128.

[0104] Axial movement of slidable member 317 along longitudinal axis 301 also pivots respective arms 322a-322d relative to one another (as indicated by unidirectional arrow 334) such that each delivery assembly 320 extends outwardly away from longitudinal axis 301 toward the GI lumen wall. For example, translation of second arm 322b toward first arm 322a via slidable member 317 causes second arm 322b to pivot about second pivot joint 324b and first arm 322a to pivot about first pivot joint 324a, as first arm 322a is in a fixed position relative to support 315. This movement, in turn, similarly pivots third arm 322c and fourth arm 322d relative to one another and to platform 326, thereby extending each delivery assembly 320 outwardly away from longitudinal axis 301. Outward extension of each delivery assembly 320 positions the delivery structure 128 adjacent to (or in engagement with) the GI lumen wall for delivery of the therapeutic compound 125 (see, e.g., Figures 10A-13B and related discussion).

[0105] During and / or after delivery of the therapeutic compound 125 from the delivery structure 128, the deflation valve is a structure that allows the gas 319 contained in the expandable member 310 to exit the device through the channel 314c and through the first support first end 314a so that the expandable member 310 can expand to help facilitate passage of the device 300 through the remainder of the intestinal tract. For example, the release means 318 is coupled to the first support first end 314a to temporarily block the channel 314c. The release means 318 can be configured to degrade at a particular rate or at a particular pH value to allow sufficient time to allow expansion of the expandable member 310 and expansion of the delivery assembly 320 for delivery of the therapeutic compound 125 before expelling a significant portion of the gas 319 contained in the expandable member 310. Additionally or alternatively, the release means 318 can be a structure that degrades, moves, or opens in response to pressure (e.g., a threshold pressure value) within the expandable member 310. Additionally or alternatively, the expandable member 310 may itself include a deflation valve, such as a flap or other structure that opens in response to internal pressure within the expandable member 310 to allow gas 319 to exit the expandable member 310. The remainder of the ingestible device 300 (e.g., delivery assembly 320, expandable member 310, support 315) can disintegrate and / or pass through the remainder of the GI tract and exit through the subject's anus.

[0106] 5A, a side cross-sectional view of an ingestible device 400 is shown including an actuator 410 (one embodiment of actuator 110) in the form of a piston 415c slidably disposed within a housing 414. In the illustrated embodiment, the actuator 410 further includes a charge 417 and an igniter 418 disposed within the housing 414 for actuating the piston 415c. In other embodiments (not shown), the actuator 410 may include one or more reactants disposed within the housing 414 for a chemical reaction to generate a gas (e.g., CO2) for actuating the piston 415c. As shown in FIG. 5A, the ingestible device 400 is shown in a first state before the ingestible device 400 reaches a desired location within the GI lumen for delivery of the therapeutic formulation 125 into the GI lumen wall or surrounding tissue. The ingestible device 400 includes a housing 402 (an embodiment of housing 102) and an outer coating 404 (an embodiment of outer coating 104). The housing 402 is configured as a capsule having a first segment 402a removably coupled to a second segment 402b.

[0107] The ingestible device 400 further includes a support 415 (one embodiment of support 115) disposed within the housing 402. The support 415 generally defines a longitudinal axis 401 of the ingestible device 400. The support 415 includes a support first end 415a and an opposing support second end 415b. The support 415 further includes a piston 415c coupled to the support 415 or formed integrally therewith. The piston 415c is located between the support first end and the second end 415a, 415b. As will be discussed in more detail below, the support 415 is movable relative to the housing 414 via the piston 415c upon actuation of the actuator 410.

[0108] The housing 414 defines a housing first end 414a having a housing first opening 414a' and a housing second end 414b having a housing second opening 414b'. The housing 414 further defines an interior including a piston chamber 414c and a reaction chamber 414d. The piston chamber 414c is defined by an inner wall portion of the housing 414 extending axially along the longitudinal axis 401. The reaction chamber 414d is defined by an inner wall portion of the housing 414 disposed adjacent to the piston chamber 414c. The reaction chamber 414d includes a charge 417 and an igniter 418 disposed therein. The charge 417 is disposed adjacent to and / or in contact with the igniter 418. The charge 417 may be a flammable material such as nitrocellulose (e.g., a nitrocellulose sheet) or a composition of other flammable materials or combinations of materials. Igniter 418 may be a coil (as shown), a conductive wire or filament (e.g., a tungsten filament), or other structure for generating heat, a spark, a flame, or other energy sufficient to ignite charge 417 in response to receiving an electrical signal (e.g., an electric current).

[0109] The housing 414 further includes electrical contacts 416 coupled to a peripheral portion of the housing 414. The electrical contacts 416 are connected to an igniter 418 and an electrical circuit 419 (shown in block diagram form in FIG. 5A ). A release means 408 (an embodiment of the release means 108) in the form of a coating or cover is applied to an outer portion of each of the electrical contacts 416 to temporarily prevent the electrical contacts 416 from contacting fluid in the GI tract in a first state shown in FIG. 5A . As described below, the electrical circuit 419 is configured to generate a signal (e.g., a current) in response to a low resistance between the electrical contacts 416 that occurs when fluid from the GI tract enters the space between the electrical contacts 416 after the release means 408 no longer covers the electrical contacts 416. The electrical circuit 419 is further configured to cause the igniter 418 to initiate combustion of the charge 417 in response to the generated signal.

[0110] For example, the electrical circuit 419 may include a power source (e.g., a battery) and one or more energy storage components (e.g., capacitors) coupled to the housing 414. The electrical circuit 419 may further include one or more additional electrical components, such as transistors, electrical switches, resistors, or other components. The electrical circuit 419 may be configured such that the electrical contacts 416 are shorted by fluid in the GI tract, allowing current from the power source to flow to the energy storage component. When a sufficient amount of current is stored in the energy storage component, the energy storage component may discharge the stored energy through the electrical circuit 419 across the igniter 418, which initiates the combustion of the charge 417.

[0111] Alternatively, the electrical circuitry 419 may include one or more sensors coupled to the housing 414 for sensing conditions within the GI tract. The electrical circuitry 419 may further include a processing circuit including a processor for executing instructions stored in a memory of the processing circuit in response to the sensed conditions to cause the igniter 418 to initiate combustion of the charge 417. For example, the one or more sensors may be coupled to the housing 414 and may be configured to sense conditions within the GI tract (e.g., pH value, temperature, electrolytic value) and generate a corresponding signal. The processor may receive the signal and, based on information stored in the memory of the processing circuit, discharge a current stored in an energy storage component, thereby causing activation of the igniter 418.

[0112] Referring again to FIG. 5A, the support 415 is at least partially disposed within and movably coupled to the housing 414 such that the piston 415c is slidably disposed within the piston chamber 414c. The piston 415c is slidably coupled to and can be sealably engaged (e.g., via one or more piston rings, seals) with an inner surface of the housing 414. In a first state shown in FIG. 5A, the support 415 extends through the housing first opening 414a' and the housing second opening 414b' such that the support first end 415a is disposed outside the housing 414 adjacent the housing first end 414a, and the support second end 415b is disposed outside the housing 414 and the housing second end 414b. The housing 414 may include one or more seals at the housing first opening 414a' and the housing second opening 414b' for sealingly engaging the support 415 to form a substantially fluid-tight seal in the piston chamber 414c and the reaction chamber 414d. The housing 414, the contacts 416, the charge 417, the igniter 418, and / or the electrical circuitry 419 may collectively define the actuator 410. As discussed below, the piston 415c moves axially within the piston chamber 414c in response to ignition of the charge 417 in the reaction chamber 414d.

[0113] Referring again to FIG. 5A, the ingestible device 400 further includes a delivery assembly 420 (an embodiment of the delivery assembly 120) pivotally coupled to the support 415. In the embodiment shown in FIG. 5A, the ingestible device 400 includes two delivery assemblies 420 disposed on opposite sides of the support 415, however, it should be understood that the ingestible device 400 may include one or more, two or more, three or more, or four or more delivery assemblies 420 according to other embodiments. The delivery assembly 420 is of similar structure to the delivery assembly 220 of FIGS. 3A-3B. Thus, for brevity, reference is made to the description of the delivery assembly 220 with respect to FIGS. 3A-3B for additional details regarding the structure and function of the delivery assembly 420.

[0114] As shown in FIG. 5A, the device 400 further includes a plurality of arms 422a-422d pivotally coupled in a cross shape by pivot joints 424a-424h to define first and second cross sections 420a, 420b of a scissor mechanism (similar to a scissor lift) configured to extend outwardly away from the longitudinal axis 401 toward the subject's GI luminal wall to deliver the therapeutic formulation 125 into the GI luminal wall, as discussed above with reference to FIGS. 3A-3B. The device 400 may include more or less than two cross sections according to other embodiments. The second arm 422b is pivotally coupled to the housing 414. The first arm 422a is pivotally coupled to the support 415 at or near the support second end 415b. The device 400 further includes a platform 426 pivotally and slidably coupled to an end of the second cross section 420b. Coupled to or integrally formed with each platform 426 is a delivery structure 128 that contains one or more therapeutic compounds 125 therein.

[0115] The ingestible device 400 further includes a stretcher 430 (an embodiment of the stretcher 130) coupled to the support 415 and the housing 414. The stretcher 430 is configured to extend axially along the longitudinal axis 401 to help orient the ingestible device 400 within the GI lumen of the subject to facilitate delivery of the therapeutic formulation 125 in a manner substantially perpendicular to the GI lumen wall. For example, the stretcher 430 includes a plurality of frame members 432a-432h pivotally coupled in a zigzag pattern by pivot joints 434a-434i to define an expandable wire frame or skeleton-like structure. The stretcher 430 can define a generally elongated structure having any suitable cross-sectional shape (e.g., circular, triangular, pentagonal, hexagonal). Additionally or alternatively, the stretcher 430 may be a hollow unitary structure including one or more concentric sides (similar to a bellows or accordion) that are expandable. The stretcher first end 430a is coupled to the support first end 415a. The stretcher second end 430b is coupled to the housing 414.

[0116] 5B, the ingestible device 400 is shown in a second state after reaching a desired location within the subject's GI lumen for delivery of the therapeutic formulation 125 from the delivery structure 128 into the wall of the subject's GI lumen. As shown in FIG. 5B, the housing 402 and / or the outer coating 404 are partially (or completely) degraded as a result of the ingestible device 400 reaching a desired location within the GI tract, which is associated with, for example, a selected or threshold pH value for triggering the degradation of the housing 402 and / or the outer coating 404. As a result of the at least partial degradation of the housing 402 and / or the outer coating 404, fluid within the GI tract is permitted to reach the interior of the housing 402 to contact the release means 408 to activate (e.g., degrade) the release means 408. In response to activation of the release means 408, the electrical contacts 416 are exposed to bodily fluids within the GI tract to cause an electrical short across the electrical contacts 416 to allow the flow of electrical current through the electrical circuit 419. The current generated by the electrical circuit 419 is sufficient to cause the igniter 418 to ignite the charge 417 to generate a combustion force within the reaction chamber 414d. The force generated within the reaction chamber 414d causes the piston 415c, and thus the support 415, to move axially along the longitudinal axis 401 toward the housing first end 414a (as shown by double-headed arrow 436). This axial movement of the support 415 causes the stretcher 430 to extend axially away from the housing 414 (as shown by double-headed arrow 436) because the stretcher first end 430a is in a fixed axial position relative to the support first end 415a and the stretcher second end 430b is coupled to the housing 414.

[0117] 5B, the axial stretching of the stretcher 430 can advantageously help to spread apart the first and second segments 402a, 402b of the capsule 402, thereby assisting in creating a substantially unobstructed area for deployment of the delivery structure 128 towards the GI lumen wall. Additionally, the axial stretching of the stretcher 430 can help to substantially align the longitudinal axis 401 with the longitudinal axis of the GI lumen at the location within the GI lumen where the stretcher 430 is actuated. Substantially aligning the longitudinal axis 401 with the longitudinal axis of the GI lumen can help to orient the delivery structure 128 substantially perpendicular to the GI lumen wall to facilitate delivery of the therapeutic formulation 125 from the delivery structure 128.

[0118] Axial movement of the support 415 along the longitudinal axis 401 relative to the housing 414 also causes each arm 422a-422d to pivot relative to one another (as indicated by unidirectional arrow 438) such that each delivery assembly 420 extends outward from the longitudinal axis 401 toward the GI lumen wall. For example, translational movement of the support 415 along the longitudinal axis 401 relative to the housing 414 causes the second arm 422b to pivot about the second pivot joint 424b and the first arm 422a to pivot about the first pivot joint 424a, because the first arm 422a is in a fixed position on the support 415 and the second arm 422b is coupled to the housing 414. This causes the third arm 422c and the fourth arm 422d to similarly pivot relative to each other and to the platform 426, thereby causing each delivery assembly 420 to extend outwardly away from the longitudinal axis 401. The outward extension of each delivery assembly 420 positions the delivery structure 128 adjacent to (or in engagement with) the GI luminal wall for delivery of the therapeutic formulation 125 into the luminal wall (see, e.g., FIGS. 10A-13B and related discussion). After delivery of the therapeutic formulation 125 from the delivery structure 128, the remainder of the ingestible device 400 (e.g., one or more of the delivery assembly 420, the housing 414, the support 415, and the extender 430) can disintegrate and / or pass through the remainder of the GI tract and out the subject's anus.

[0119] For ease of reference, certain components above (or below) the support 415 are indicated with numerical callouts in FIGS. 5A-5B, whereas similar components below (or above) the support 415 are not indicated with numerical callouts, although it should be understood that similar components located above and below the support 415 are referenced with similar callouts.

[0120] Referring to FIG. 6A, a side cross-sectional view of an ingestible device 500 including an actuator in the form of a motor 510 (one embodiment of actuator 110) is shown. In the illustrated embodiment, motor 510 is a screw-type rotary motor. In another embodiment (not shown), motor 510 is a linear motor. As shown in FIG. 6A, ingestible device 500 is illustrated in a first state before ingestible device 500 reaches a desired location within the GI lumen for delivering therapeutic formulation 125 into the GI lumen wall. Ingestible device 500 includes a housing 502 (an embodiment of housing 102) and an outer coating 504 (an embodiment of outer coating 104). Housing 502 is configured as a capsule having a first segment 502a removably coupled to a second segment 502b.

[0121] Ingestible device 500 further includes a support 515 (one embodiment of support 115) disposed within housing 502. Support 515 defines a general longitudinal axis 501 of ingestible device 500. Support 515 includes a support first end 515a and a support second end 515b opposite support first end 515a. Support 515 further includes an external threaded portion 515c located between first and second ends 515a, 515b. Threaded portion 515c can extend along at least a portion of support 515 or along the entire length of support 515. Threaded portion 515c is threadedly coupled to motor 510 such that support 515 extends through and is movable relative to motor 510. As described in more detail below, the support 515 is structured to translate along the longitudinal axis 501 via rotational movement of the threaded portion 515c relative to the motor 510 upon actuation of the motor 510. In another embodiment (not shown), the support 515 includes a linear gear that functions as a rack, and the motor 510 includes a rotating gear that functions as a pinion that is rotatably coupled to the linear gear to translate the support 515 relative to the motor 510 along the longitudinal axis 501.

[0122] Referring again to FIG. 6A, the motor 510 is a screw-type rotary motor including a motor housing 510a and a rotatable shaft 510b. The motor 510 may be an electric motor (e.g., a micro direct current (DC) motor, a synchronous or asynchronous motor, a micro alternating current (AC) motor, a stepper motor, or a servo motor), a nanomotor, a magnetic motor, or any other type of microscale rotary motor that can be housed within the capsule 502. The rotatable shaft 510b is rotatable relative to the motor housing 510a upon actuation of the motor 510. The rotatable shaft 510b is hollow and includes an internal thread that is complementary to an external thread 515c of the support 515 such that the support 515 can be threadably coupled to the rotatable shaft 510b. The motor housing 510a includes electrical contacts 516 and an electrical circuit 519 (shown in block diagram form) operably coupled to the electrical contacts 516. 6A, a release means 508 (an embodiment of release means 108) in the form of a coating or cover is disposed over the electrical contacts 516 to temporarily prevent contact with fluid in the GI tract. For example, the release means 508 may be a degradable coating or layer of material that substantially covers an outer portion of the electrical contacts 516. For example, the electrical circuit 519 may include a power source (e.g., a battery) coupled to the motor 510 and one or more additional electrical components for providing an electrical current that operates the motor 510 in response to an electrical short to rotate the rotatable shaft 510b.

[0123] Still referring to FIG. 6A, the ingestible device 500 further includes a delivery assembly 520 (an embodiment of the delivery assembly 120) pivotally coupled to the support 515. In the embodiment shown in FIG. 6A, the ingestible device 500 includes two delivery assemblies 520 disposed on opposite sides of the support 515, however, it should be understood that the ingestible device 500 may include one or more, two or more, three or more, or four or more delivery assemblies 520 according to other embodiments. The delivery assembly 520 is of the same structure as the delivery assembly 220 of FIGS. 3A-3B. Thus, for the sake of brevity, reference is made to the description of the delivery assembly 220 with respect to FIGS. 3A-3B for additional details regarding the structure and function of the delivery assembly 520.

[0124] As shown in FIG. 6A, the device 500 further includes a plurality of arms 522a-522d pivotally coupled in a cross shape by respective pivot joints 524a-524h to define first and second cross sections 520a, 520b of a scissor mechanism (similar to a scissor lift) configured to extend outwardly away from the longitudinal axis 501 toward a luminal wall in the GI tract of the subject to deliver the therapeutic formulation 125, as discussed above with reference to FIGS. 3A-3B. The device 500 may include more or less than two cross sections according to other embodiments. The first arm 522a is pivotally coupled to a first rotatable member 517a by a first pivot joint 524a. The first rotatable member 517a is rotatably coupled to the support 515 but is axially fixed relative to the support 515 at or near the support second end 515b. The second arm 422b is pivotally coupled to the support 515 via a second rotatable member 517b. The second rotatable member 517b is movably (e.g., slidably) coupled to the support 515 and configured to allow the support 515 to translate and rotate relative to the second rotatable member 517b. The first rotatable member 517a and the second rotatable member 517b may be configured as bushings, rotation bearings, sleeves, or similar components. The device 500 further includes a platform 526 pivotally and slidably coupled to an end of the second cross 520b. A delivery structure 128 having one or more therapeutic compounds 125 therein is coupled to or integrally formed with each platform 526.

[0125] The ingestible device 500 further includes a stretcher 530 (an embodiment of the stretcher 130) coupled to the support 515 and the motor housing 510a. The stretcher 530 is structured to extend axially along a longitudinal axis 501 to help orient the ingestible device 500 within the GI lumen of the subject to facilitate delivery of the therapeutic formulation 125 in a manner substantially perpendicular to the GI lumen wall. For example, the stretcher 530 includes a plurality of linear frame members 532a-h pivotally coupled in a zigzag pattern by respective pivot joints 534a-i to define an expandable wire frame or skeleton-like structure. The stretcher 230 can define a generally elongated structure having any suitable cross-sectional shape (e.g., circular, triangular, pentagonal, hexagonal). Additionally or alternatively, the stretcher 530 may be a hollow monolithic structure including one or more concentric sides that are expandable (similar to a bellows or accordion). The stretcher first end 530a is coupled to a third rotatable member 517c, which is rotatably coupled to the support 515 at or near the support first end 515a. The third rotatable member 517c may be of similar structure to the first and second rotatable members 517a, 517b. The stretcher second end 530b is coupled to the second rotatable member 517b (e.g., via a second pivot joint 524b). Although the expander 530 is shown disposed above the release means 508 and motor 510, it should be understood that the release means 508 may be accessible through one or more openings in the expander 530 to allow actuation of the release means 508 (e.g., disintegration by contact with fluid in the GI tract).

[0126] 6B, the ingestible device 500 is shown in a second state when the ingestible device 500 reaches a desired location within the GI lumen of the subject for delivery of the therapeutic formulation 125 from the delivery structure 128 to the wall of the GI lumen of the subject. As shown in FIG. 6B, the housing 502 and / or the outer coating 504 are partially (or completely) degraded as a result of the ingestible device 500 reaching a desired location within the GI tract, which is associated, for example, with a selected or threshold pH value for triggering the degradation of the housing 502 and / or the outer coating 504. As a result of the at least partial degradation of the housing 502 and / or the outer coating 504, fluid within the GI tract is permitted to reach the interior of the housing 502 to contact the release means 508 to activate (e.g., degrade) the release means 508. In response to activation of the release means 508, the fluid within the GI tract creates an electrical short across the electrical contacts 516 such that an electrical current flows through the electrical circuit 519. The current from the electrical circuit 519 is sufficient to actuate the motor 510 to generate a rotational force that rotates the rotatable shaft 510a about the longitudinal axis 501 (as indicated by the rotational arrow 536). This rotational movement of the rotatable shaft 510b rotates the support 515 about the longitudinal axis 401 and moves axially along the longitudinal axis 401 via threaded engagement with the threaded portion 515. This axial movement of the support 515 causes the stretcher 530 to extend axially away from the motor 510, since the stretcher first end 530a is at a fixed axial position relative to the motor housing 510a and the stretcher second end 530b is rotatably coupled to the support first end 515a at a fixed axial position on the support 515.

[0127] 6B, the axial stretching of the stretcher 530 can advantageously help to push apart the first and second segments 502a, 502b of the capsule 502 (as indicated by the double arrows 538), thereby creating a substantially unobstructed area for deployment of the delivery structure 128 towards the GI lumen wall. Additionally, the axial stretching of the stretcher 530 can help to substantially align the longitudinal axis 501 with the longitudinal axis of the GI lumen at a location within the GI lumen where the stretcher 530 is actuated. Substantially aligning the longitudinal axis 501 with the longitudinal axis of the GI lumen can advantageously help to orient the delivery structure 128 substantially perpendicular to the GI lumen wall to facilitate delivery of the therapeutic formulation 125 from the delivery structure 128 to the lumen wall.

[0128] Axial movement of support 515 along longitudinal axis 501 relative to motor 510 also causes respective arms 522a-522d to pivot relative to one another (as indicated by unidirectional arrow 539) such that each delivery assembly 520 extends outward from longitudinal axis 501 toward the GI lumen wall. For example, translational movement of support 515 along longitudinal axis 501 relative to motor 510 causes second arm 522b to pivot about second pivot joint 524b and first arm 522a to pivot about first pivot joint 524a, since second arm 522b can translate relative to support 515 via second rotatable member 517b and first arm 522a is axially fixed to support 515 via first rotatable member 517a. This, in turn, causes the third arm 522c and the fourth arm 522d to similarly pivot relative to each other and to the platform 526, thereby causing each delivery assembly 520 to extend outwardly away from the longitudinal axis 501. The outward extension of each delivery assembly 520 positions the delivery structure 528 adjacent to (or in engagement with) the GI luminal wall for delivery of the therapeutic formulation 125 into the luminal wall (see, e.g., FIGS. 10A-13B and related discussion). After delivery of the therapeutic formulation 125 from the delivery structure 128, the remainder of the ingestible device 500 (e.g., one or more of the delivery assembly 520, the motor 510, the support 515, and the extender 530) can disintegrate and / or pass through the remainder of the GI tract and out the subject's anus.

[0129] For ease of reference, certain components above (or below) the support 515 are indicated with numerical callouts in FIGS. 6A-6B, whereas similar components below (or above) the support 515 are not indicated with numerical callouts, although it should be understood that similar components located above and below the support 515 are referenced with similar callouts.

[0130] 7A, there is shown a side cross-sectional view of an ingestible device 600 including an actuator 610 (one embodiment of actuator 110) in the form of a piston 615c slidably disposed within a housing 614. In the illustrated embodiment, the actuator 610 further includes a hydrogel 618 disposed within the housing 614 for actuating the piston 615c. As shown in FIG. 7A, the ingestible device 600 is illustrated in a first state before the ingestible device 600 reaches a desired location within the GI lumen for delivering the therapeutic formulation 125 into the GI lumen wall. The ingestible device 600 includes a housing 602 (an embodiment of housing 102) and an outer coating 604 (an embodiment of outer coating 104). The housing 602 is configured as a capsule having a first segment 602a removably coupled to a second segment 602b.

[0131] Ingestible device 600 further includes a support 615 (one embodiment of support 115) disposed within housing 602. Support 615 generally defines a longitudinal axis 601 of ingestible device 600. Support 615 includes a support first end 615a and a support second end 615b opposite support first end 615a. Support 615 further includes a piston 615c coupled to support 615 or integrally formed therewith. Piston 615c is located between support first and second ends 615a, 615b. As discussed in more detail below, support 615 is movable relative to housing 614 via piston 615c upon actuation of actuator 610.

[0132] The housing 614 can form a portion of the actuator 610. The housing 614 defines a housing first end 614a having a housing first opening 614a' and a housing second end 614b having a housing second opening 614b'. The housing 614 further defines an interior including a piston chamber 614c. The piston chamber 614c is defined by an inner surface of the housing 614 extending axially along the longitudinal axis 601. The hydrogel 618 is disposed in front of, adjacent to, and / or in contact with the piston 615c near the housing second opening 614b within the piston chamber 614c. In the illustrated embodiment, the hydrogel 618 is a three-dimensional polymer configured to swell or expand within the piston chamber 614c in response to a stimulus within the GI tract, such as a fluid within the GI tract having a threshold pH value, or range of pH values, associated with a particular location within the GI tract for delivery of the therapeutic formulation 125. For example, hydrogel 618 may include one or more polyelectrolytes that are pH responsive. Additionally or alternatively, hydrogel 618 may include one or more polymers that are responsive to temperature, light, ionic strength, or other types of stimuli associated with a particular location in the GI tract (e.g., small intestine). Hydrogel 618 may be in the form of a film, gel, or other physical structure having a variety of shapes and configurations that can be disposed within piston chamber 614c.

[0133] The housing 614 further includes a plurality of openings 614d-g disposed along the circumference of the housing 614. The openings 614d-g are spaced apart from one another and distributed along the axial length of the housing 614. The openings 614d-g are structured to provide a fluid pathway from the GI luminal environment to the piston chamber 614c and cause progressive actuation of the hydrogel 618. In the first state shown in FIG. 7A, the first pair of openings 614d located closest to the housing second end 614b adjacent the hydrogel 618 is temporarily blocked by the release means 608 (one embodiment of the release means 108). The release means 608 may be a degradable release means configured as a plug or similar structure to temporarily block the first pair of openings 618d. As discussed below, upon actuation of the release means 608 (e.g., disintegration due to contact with fluids in the GI tract), fluids from the GI lumen environment are permitted to enter the piston chamber 614c and contact and expand the hydrogel 618, thereby moving the piston 615c axially along the longitudinal axis 601 toward the housing first end 614a. As discussed in more detail below, as the initial expansion of the hydrogel 618 causes the piston 615c to move axially toward the first end 614a, the cover 636 coupled to or integrally formed with the stretcher 630 (embodiment of the stretcher 130) moves away from the housing 414, progressively exposing the openings 614e-614g to allow additional fluids from the GI lumen environment to contact the hydrogel 618, thereby causing progressive actuation of the hydrogel 618 within the piston chamber 614c. Alternatively, the cover 636 may be coupled to the support 615.

[0134] Still referring to FIG. 7A, the support 615 is disposed within the housing 614 and movably coupled to the housing 614 such that the piston 615c is slidably disposed within the piston chamber 614c. The piston 615c is disposed in front of the hydrogel 618 near the housing second end 614b. The piston 615c is slidably coupled to the inner surface of the housing 414 and can be sealably engaged (e.g., via one or more piston rings, seals). The support 615 extends through the housing first opening 614a and the housing second opening 614b such that in the first state shown in FIG. 7A, the support first end 615a is disposed outside the housing 614 adjacent the housing first end 614a and the support second end 615a is disposed outside the housing 614 near the housing second end 614b. The housing 614 can include one or more seals at the housing first opening 614a' and the housing second opening 614b' for sealingly engaging the support 615 to form a substantially fluid-tight seal within the piston chamber 614c. The housing 614, the piston 615c, and / or the hydrogel 618 can collectively define the actuator 610.

[0135] Referring again to FIG. 7A, the ingestible device 600 further includes a delivery assembly 620 (an embodiment of the delivery assembly 120) pivotally coupled to the support 615 and the housing 614. In the embodiment shown in FIG. 7A, the ingestible device 600 includes two delivery assemblies 620 disposed on opposite sides of the support 615, however, it should be understood that the ingestible device 600 may include one or more, two or more, three or more, or four or more delivery assemblies 620 according to other embodiments. The delivery assembly 620 is of similar structure to the delivery assembly 220 of FIGS. 3A-3B. Thus, for the sake of brevity, reference is made to the description of the delivery assembly 220 with respect to FIGS. 3A-3B for additional details regarding the structure and function of the delivery assembly 620.

[0136] As shown in FIG. 7A, the device 600 further includes a plurality of arms 622a-622d pivotally coupled in a cross shape by respective pivot joints 624a-624h to define first and second cross sections 620a, 620b of a scissor mechanism (similar to a scissor lift) configured to extend outwardly away from the longitudinal axis 601 toward the subject's GI luminal wall to deliver the therapeutic formulation 125 into the GI luminal wall, as discussed above with reference to FIGS. 3A-3B. The device 600 may include more or less than two cross sections according to other embodiments. The first arm 622a is pivotally coupled to the support 615 at or near the support second end 615b. The second arm 622b is pivotally coupled to the housing 614 at or near the housing second end 614b. The device 600 further includes platforms 626 pivotally and slidably coupled to an end of the second cross portion 620b. Coupled to or integrally formed with each platform 626 is a delivery structure 628 that includes one or more therapeutic compounds 125 therein.

[0137] The ingestible device 600 further includes a stretcher 630 (an embodiment of the stretcher 130) coupled to the support 615 and the housing 614. The stretcher 630 is structured to extend axially along the longitudinal axis 601 to help orient the ingestible device 600 within the GI lumen of the subject, which can help facilitate delivery of the therapeutic formulation 125 in a manner substantially perpendicular to the GI lumen wall. For example, the stretcher 630 includes a plurality of linear frame members 632a-632h pivotally coupled in a zigzag pattern by respective pivot joints 634a-634i (e.g., pins, ball-and-socket joints, spring joints) to define an expandable wire frame or skeleton-like structure. The stretcher 630 can define a generally elongated structure having any suitable cross-sectional shape (e.g., circular, triangular, pentagonal, hexagonal). Additionally or alternatively, the stretcher 630 may be a hollow unitary structure including one or more concentric sides that are expandable (similar to a bellows or accordion). The stretcher first end 630a is coupled to the housing 614. The stretcher second end 630b is coupled to the support first end 615a.

[0138] The cover 636 is coupled to the stretcher 630 or is integrally formed therewith. The cover 636 is disposed over a portion of the housing 614 such that the cover 636 temporarily blocks the openings 614e-614g to prevent fluid from the GI lumen environment from entering the piston chamber 614c. The cover 636 can be structured as a sleeve or other type of cover. The cover 636 is configured to move relative to the housing 614 in response to axial movement of the stretcher 630 to selectively expose the openings 614e-614g and allow fluid from the GI lumen environment to enter the piston chamber 614c. Additionally or alternatively, the cover 636 can be coupled to the support 615 such that axial movement of the support 615 moves the cover 636 directly relative to the housing 614. In this manner, the cover 636 can enable incremental actuation of the hydrogel 618.

[0139] 7B, the ingestible device 600 is shown in a second state in which the ingestible device 600 has reached a desired location within the GI lumen of the subject for delivery of the therapeutic formulation 125 from the delivery structure 128 into the wall of the GI lumen of the subject. As shown in FIG. 7B, the housing 602 and / or the outer coating 604 are partially (or completely) degraded as a result of the ingestible device 600 reaching a desired location within the GI tract, which is associated, for example, with a selected or threshold pH value for triggering the degradation of the housing 602 and / or the outer coating 604. As a result of the at least partial degradation of the housing 602 and / or the outer coating 604, fluid within the GI tract is permitted to reach the interior of the housing 602 to contact the release means 608 to activate (e.g., degrade) the release means 608. In response to actuation of the release means 608, fluid within the GI tract is permitted to enter the piston chamber 614 via a first opening 614d disposed adjacent the hydrogel 618 to cause an initial expansion or swelling of the hydrogel 618. The expansion of the hydrogel 618 causes the piston 615c to move axially along the longitudinal axis 601 toward the housing first end 614a, thereby moving the support 615 axially in the same direction relative to the housing 614. As the piston 615c moves axially toward the housing first end 614a, the extender 630 extends axially and the cover 636 moves away from the housing 614, exposing additional openings 614e-614g on the housing 614 to allow additional fluid from the GI lumen environment to enter the piston chamber 614c and contact the hydrogel 618. Additional fluid entering piston chamber 614 c causes progressive expansion of hydrogel 618 and subsequent axial movement of support 615 .

[0140] 7B, the axial stretching of the stretcher 630 can advantageously help to spread apart the first and second segments 602a, 602b of the capsule 602 (as indicated by the bidirectional arrow 636), thereby creating a substantially unobstructed area for deployment of the delivery structure 628 towards the GI lumen wall. Additionally, the axial stretching of the stretcher 630 can help to substantially align the longitudinal axis 601 with the longitudinal axis of the GI lumen at a location within the GI lumen where the stretcher 630 is actuated. Substantially aligning the longitudinal axis 601 with the longitudinal axis of the GI lumen can help to orient the delivery assembly 620 substantially perpendicular to the GI lumen wall, which can facilitate delivery of the therapeutic formulation 125 from the delivery structure 628.

[0141] Axial movement of the support 615 along the longitudinal axis 601 relative to the housing 614 also causes each arm 622a-622d to pivot relative to one another such that each delivery assembly 620 extends outward from the longitudinal axis 601 toward the GI lumen wall (as indicated by unidirectional arrow 638). For example, axial movement of the support 615 along the longitudinal axis 601 relative to the housing 614 causes the second arm 622b to pivot about the second pivot joint 624b and the first arm 622a to pivot about the first pivot joint 624a, since the first arm 422a is coupled to the movable support 615 and the second arm 622b is at a fixed axial position on the housing 614. This, in turn, causes the third arm 622c and the fourth arm 622d to similarly pivot relative to one another and to the platform 626, thereby extending each delivery assembly 620 outwardly away from the longitudinal axis 601. The outward extension of each delivery assembly 620 positions the delivery structure 628 adjacent to (or in engagement with) the GI lumen wall for delivery of the therapeutic formulation 125 (see, e.g., FIGS. 10A-13B and related discussion). After delivery of the therapeutic formulation 125 from the delivery structure 628, the remainder of the ingestible device 600 (e.g., one or more of the delivery assembly 620, the housing 614, the support 615, and the extender 630) can disintegrate and / or pass through the remainder of the GI tract and out the subject's anus.

[0142] For ease of reference, certain components above (or below) the support 615 are indicated with numerical callouts in FIGS. 7A-7B, whereas similar components below (or above) the support 615 are not indicated with numerical callouts, although it should be understood that similar components located above and below the support 615 are referenced with similar callouts.

[0143] 8A-9B, additional or alternative embodiments of the delivery assembly 120 are shown in the form of delivery assemblies 720, 820. The delivery assemblies 720, 820 are structured to be coupled to a support via a pivotable arm configured to pivot relative to the support about a pivot axis defined by a pivot joint (e.g., a pin, hinge, ball-and-socket, spring joint). The delivery assemblies 720, 820 can be used in any of the previous embodiments in combination with any one or combination of the release means, actuators, and / or extenders described above with reference to FIGS. 3A-7B. As such, the corresponding release means 108, actuator 110, and extender 130 of each device are depicted in block diagram form in FIGS. 8A-9B.

[0144] 8A, there is shown a side cross-sectional view of an ingestible device 700 including a delivery assembly 720 (an embodiment of delivery assembly 120) in the form of a pivotable arm 722. As shown in FIG. 8A, the ingestible device 700 is illustrated in a first state before the ingestible device 700 reaches a desired location within the GI lumen for delivering a therapeutic formulation 125 into the GI lumen wall. The ingestible device 700 further includes a housing 702 (an embodiment of housing 102) and an outer coating 704 (an embodiment of outer coating 104). The housing 702 is configured as a capsule having a first segment 702a removably coupled to a second segment 702b.

[0145] Ingestible device 700 further includes support 715 (one embodiment of support 115). Support 715 is a generally elongate member that defines a general longitudinal axis 701 of ingestible device 700. Support 715 includes a support first end 715a and a support second end 715b opposite support first end 715a. Support 715 can have any one or combination of the structural configurations of support 115 described above with reference to the embodiment of Figures 3A-7B.

[0146] The ingestible device 700 further includes a delivery assembly 720 (an embodiment of the delivery assembly 120) pivotally coupled to the support 715. In the embodiment shown in FIG. 8A, the ingestible device 700 includes two delivery assemblies 720 disposed on opposite sides of the support 715, however, it should be understood that the ingestible device 700 may include one or more, two or more, three or more, or four or more delivery assemblies 720 according to other embodiments. Each delivery assembly 720 includes a pivotable arm 722. Although the pivotable arms 722 are shown as substantially linear members, the pivotable arms 722 may be configured to be substantially non-linear or may include substantially non-linear portions according to other embodiments. A first end of the pivotable arm 722 is pivotally coupled to the support 715 at or near the support second end 715b via a first pivot joint 724a. A second, opposite end of the pivotable arm 722 is pivotally coupled by a second pivot joint 724b to a delivery structure 728 that contains therein one or more therapeutic compounds 125. The delivery structure 728 is shown in block diagram form in Figures 8A-8B, although various embodiments of the delivery structure 728 are described below with reference to Figures 10A-13B.

[0147] Still referring to FIG. 8A, each delivery assembly 720 further includes a rib 723 pivotally coupled at a first end to the pivotable arm 722 via a third pivot joint 724c between both ends of the pivotable arm 722. The rib 723 is a substantially linear member, although the rib 723 may be a structure that is substantially non-linear or includes a substantially non-linear portion according to other embodiments. The rib 723 includes an opposite second end pivotally coupled to the slidable member 725 by a fourth pivot joint 724d. The various pivot joints 724a-724d may be of similar structure to any of the other pivot joints previously described herein. The slidable member 725 may be a hub, sleeve, bushing, or other similar structure that is translatable (e.g., slidable) relative to the support 715 along the longitudinal axis 701. The ingestible device 700 is configured such that actuation of the actuator 710 causes the slidable member 725 to translate axially along the longitudinal axis 701 relative to the support 715 toward the support second end 715b, thereby causing each delivery assembly 720 to pivot about the first pivot axis 724a and extend outward from the support 715 toward the GI lumen wall to deliver the therapeutic formulation 125 from the delivery structure 128.

[0148] For example, referring to FIG. 8B, the ingestible device 700 is shown in a second state when it reaches a desired location within the GI lumen of a subject for delivery of the therapeutic formulation 125 from the delivery structure 128 to the GI lumen wall. As shown in FIG. 8B, the housing 702 and / or the outer coating 704 are partially (or completely) degraded as a result of the ingestible device 700 reaching a desired location within the GI tract, which is associated, for example, with a selected or threshold pH value for triggering the degradation of the housing 702 and / or the outer coating 704. As a result of the at least partial degradation of the housing 702 and / or the outer coating 704, fluid within the GI tract is permitted to reach the interior of the housing 702 to contact the release means 108 to activate (e.g., degrade) the release means 108. In response to actuation of the release means 108, the actuator 110 is actuated to axially extend the stretcher 130 along the longitudinal axis 701 and axially translate the slidable member 725 (as indicated by unidirectional arrow 736) along the longitudinal axis 701 toward the support second end 715b. This axial movement of the slidable member 725 causes each rib 723 to pivot relative to the slidable member 725 and to the respective pivotable arm 722, which in turn causes the pivotable arm 722 to pivot about the first pivot joint 724a (indicated by rotational arrow 738) and extend outwardly away from the support 115, similar to the function of an umbrella. The outward movement of the pivotable arm 722 positions the delivery structure 728 adjacent (or in contact with) the GI luminal wall, enabling delivery of the therapeutic formulation 125 to the luminal wall (see, e.g., FIGS. 10A-13B and related discussion). Additionally, outward movement of the pivotable arms 722 can aid in separation of the first and second segments 702a, 702b of the capsule 702 (as indicated by double arrow 739).

[0149] 9A, there is shown a side cross-sectional view of an ingestible device 800 including a delivery assembly 820 (an embodiment of delivery assembly 120) in the form of a pivotable arm 822. As shown in FIG. 9A, the ingestible device 800 is illustrated in a first state before the ingestible device 800 reaches a desired location within the GI lumen for delivering a therapeutic formulation 125 into the GI lumen wall. The ingestible device 800 further includes a housing 802 (an embodiment of housing 102) and an outer coating 804 (an embodiment of outer coating 104). The housing 802 is configured as a capsule having a first segment 802a removably coupled to a second segment 802b.

[0150] Ingestible device 800 further includes support 815 (an embodiment of support 115). Support 815 is a generally elongate member that defines a general longitudinal axis 801 of ingestible device 800. Support 815 includes support first end 815a and support second end 815b opposite support first end 815a. Support 815 can have any one or combination of the structural configurations of support 115 described above with reference to Figures 3A-7B.

[0151] The ingestible device 800 further includes a delivery assembly 820 (an embodiment of the delivery assembly 120) pivotally coupled to the support 815. In the embodiment shown in FIG. 9A, the ingestible device 800 includes two delivery assemblies 820 disposed on opposite sides of the support 815, however, it should be understood that the ingestible device 800 may include one or more, two or more, three or more, or four or more delivery assemblies 820 according to other embodiments. Each delivery assembly 820 includes a pivotable arm 822. Although the pivotable arms 822 are shown as substantially linear members, the pivotable arms 822 may be substantially non-linear or include substantially non-linear portions according to other embodiments. A first end of the pivotable arm 822 is pivotally coupled to the support 815 at or near the support second end 815b via a first pivot joint 824a. An opposite second end of the pivotable arm 822 is pivotally coupled by a second pivot joint 824b to a delivery structure 128 that contains therein one or more therapeutic compounds 125. The delivery structure 128 and therapeutic compound 125 are shown in block diagram form in Figures 9A-9B, although various embodiments of the delivery structure 128 and therapeutic compound 125 are described below with reference to Figures 10A-13B.

[0152] 9A , the ingestible device 800 further includes a wedge 825 movably coupled to the support 815. The wedge 825 has a generally conical shape and is movable (e.g., slidable) relative to a surface of the support 815 such that the wedge can translate relative to the support 815 along the longitudinal axis 801. As discussed in more detail below, the ingestible device 800 is configured such that actuation of the actuator 810 causes the wedge 825 to translate axially along the longitudinal axis 801 relative to the support 815 toward the support second end 815b, thereby causing each delivery assembly 820 to pivot about the first pivot axis 824a and extend outwardly from the support 815 toward the GI lumen wall to deliver the therapeutic formulation 125.

[0153] For example, referring to FIG. 9B, ingestible device 800 is shown in a second state when it reaches a desired location within the subject's GI lumen for delivery of therapeutic formulation 125 from delivery structure 828 into the wall of the subject's GI lumen. As shown in FIG. 9B, housing 802 and / or outer coating 804 are partially (or completely) degraded as a result of ingestible device 800 reaching a desired location within the GI tract, which is associated with, for example, a selected or threshold pH value to trigger degradation of housing 802 and / or outer coating 804. As a result of at least partial degradation of housing 802 and / or outer coating 804, fluid within the GI tract is permitted to reach the interior of housing 802 to contact release means 108 to activate (e.g., degrade) release means 108. In response to actuation of the release means 108, the actuator 110 is actuated to axially extend the extender 130 along the longitudinal axis 801 and axially translate the wedge 825 along the longitudinal axis 801 relative to the support 815 toward the support second end 815b (as indicated by unidirectional arrow 836). The wedge 825 can thereby contact the pivotable arm 722 and push the pivotable arm 722 to pivot the pivotable arm 722 about the first pivot joint 724a (as indicated by rotational arrow 838) and extend outwardly away from the support 815, similar to the function of an umbrella. The cone shape of the wedge 825 can advantageously function to push the pivotable arm 722 outwardly as the wedge 825 moves axially toward the support second end 815b. Outward movement of the pivotable arms 822 positions the delivery structure 828 adjacent (or in contact with) the GI luminal wall to enable delivery of the therapeutic formulation 125 to the luminal wall (see, e.g., FIGS. 10A-13B and related discussion). Additionally, outward movement of the pivotable arms 822 can aid in separation of the first and second segments 802a, 802b of the capsule 802 (as indicated by double arrow 839).

[0154] Each of the delivery assemblies 720, 820 may include a retention feature (e.g., hooks, barbs, sharp protrusions) coupled to or integrally formed with each delivery structure 128 for engaging with a GI lumen wall to reorient the delivery structure 128 relative to the lumen wall to facilitate delivery of the therapeutic formulation 125. For example, the retention feature of each delivery structure 128 may engage tissue of the lumen wall to temporarily retain the delivery structure 128 against the lumen wall. The temporary retention of the delivery structure 128 may cause the delivery structure 128 to pivot relative to the pivotable arms 722, 822 via the second pivot joints 724b, 824b, respectively, thereby allowing the delivery structure 128 to be reoriented relative to the lumen wall as the ingestible device 700, 800 moves through the GI tract (e.g., via peristaltic action of the GI lumen). The delivery structure 128 can be reoriented such that the therapeutic formulation 125 can be delivered in a direction substantially perpendicular to the GI lumen wall upon ejection from the delivery structure 128. Additionally, temporary retention of the delivery structure 128 can help provide sufficient time for the therapeutic formulation 125 to eject into the lumen wall.

[0155] 10A-13B, various embodiments of the delivery structure 128 are shown. It should be understood that the various delivery structures described in the following paragraphs can be used with any one of the embodiments of the delivery assembly 120 previously described herein (e.g., delivery assemblies 220, 320, 420, 520, 620, 720, 820), or combinations thereof. For example, the various delivery structures described herein can be coupled to or integrally formed with a platform (e.g., platform 226, 326, 426, 526, 626). In other embodiments, the various delivery structures may be pivotally coupled directly to a pivotable arm (e.g., pivotable arm 722, 822). Additionally, although the delivery structures below are depicted with a single therapeutic formulation disposed therein, the various delivery structures may be structures that include multiple therapeutic formulations for delivery into the GI lumen wall or surrounding tissue.

[0156] In the following embodiments, the therapeutic compound 125 is configured as an elongated member having a tapered end for penetrating the seal of the container and penetrating the GI lumen tissue. A second end of the therapeutic compound 125 opposite the tapered end defines an engagement surface for engaging with an actuation mechanism / second actuator (e.g., protrusion, piston) of the delivery structure 128 to expel the therapeutic compound 125 from the container. The engagement surface may be generally planar or may include a structure with a complementary shape to a portion of the actuation mechanism to facilitate the transmission of force from the actuation mechanism to the therapeutic compound 125. It should be understood that the therapeutic compound 125 may be of different structures according to other embodiments and is not limited to the following description.

[0157] 10A shows a side cross-sectional view of a delivery structure 140 (an embodiment of the delivery structure 128) for use in one or more embodiments of the delivery assembly 120 in the present disclosure. The delivery structure 140 includes a holder 142, a container 144, and a therapeutic formulation 145 (an embodiment of the therapeutic formulation 125) disposed within the container 144. The delivery structure 140 is shown in a first state prior to reaching a desired location within the GI lumen for delivery of the therapeutic formulation 145 within the GI lumen wall. As described below, the delivery structure 140 is a structure that delivers the therapeutic formulation 145 from the container 144 into the GI lumen wall. For example, the delivery structure 140 relies on an external force applied to the delivery structure 140 to expel the therapeutic formulation 145 into the lumen wall instead of using a separate actuator to actively deliver the therapeutic formulation 145.

[0158] Still referring to FIG. 10A, the holder 142 includes a peripheral wall 142a that defines an interior 142c. The holder 142 further includes a protrusion 142b that extends from a lower interior portion of the peripheral wall 142a within the interior 142c. The protrusion 142b is sized and positioned within the interior 142c to define a circumferential opening 142c' that surrounds the sides of the protrusion 142b. The holder 142 further includes an open end 142d opposite the protrusion 142b for penetrating the container 144 and receiving it within the interior 142c. The protrusion 142b includes a tapered (e.g., pointed) end for penetrating a seal of the container 142 to expel the therapeutic formulation 145 therefrom to the GI lumen wall, as discussed in further detail below. The protrusion 142b extends to a height below the open end 142d such that the protrusion 142b is disposed within the interior 142c. The holder 142 further includes one or more nubs 142e or other structural features that extend inwardly from an inner side of the peripheral wall 142a. The nubs 142e are structures that provide an interference fit with the container 144 to temporarily hold the container 144 in place relative to the holder 142.

[0159] The container 144 is structured to contain the therapeutic compound 145 therein and temporarily protect the therapeutic compound 145 from degradation in the GI tract. The container 144 is further structured to be movably coupled to the holder 142. The container 144 includes a body 144a defining an interior 144a', a first open end 144a'', and a second open end 144a''' opposite the first open end 144a''. The therapeutic compound 145 is disposed within the interior 144a'. A first seal 144b is coupled to the body 144a at the first open end 144a'', and a second seal 144c is coupled to the body 144a at the second open end 144a''', such that the interior 144a' is substantially sealed from fluids to temporarily protect the therapeutic compound 145 from degradation. The first seal 144b and the second seal 144c are formed from a pierceable material to allow the protrusions 142b and the therapeutic compound 145 to pierce / penetrate therethrough. For example, the first and second seals 144b, 144c can be a pierceable film, such as aluminum foil, that is bonded (e.g., using an adhesive) to the body 144a.

[0160] The body 144a is movably (e.g., slidably) coupled to the inner side of the peripheral wall 142a. The container 144 is at least partially disposed in the interior 142c such that the second seal 144c is disposed adjacent to the tapered end of the protrusion 142b. The container 144 extends outwardly from the holder 142 through the opening 142d such that the first seal 144b defines the outermost portion of the delivery structure 140 in the first state shown in FIG. 10A. The nub 142e can engage a complementary feature (e.g., recess, opening, protrusion) on the container 144 to temporarily hold the container 144 in place relative to the holder 142 via an interference state. As described below, the container 144 is configured to move (e.g., slide) relative to the holder 142 in response to contact with the GI lumen wall to deliver the therapeutic formulation 145 from the container 144 into the GI lumen wall.

[0161] 10B, for example, the delivery structure 140 is shown in a second state when the delivery structure 140 is moved into contact with the GI lumen wall via outward extension of the delivery assembly 120 (upon actuation of the actuator 110, as indicated by unidirectional arrow 146). The return force from the container 144 contacting the GI lumen wall is sufficient to overcome the interference condition between the container 144 and the nub 142e of the holder 142, causing the container 144 to be moved inwardly within the interior 142c toward the protrusion 142b. This inward movement of the container 144 causes the protrusion 142b to penetrate the second seal 144c and contact the engagement surface of the therapeutic compound 145, thereby discharging the therapeutic compound 145 from the container 144 through the first seal 144b and into the GI lumen wall or surrounding tissue, where one or more therapeutic agents of the therapeutic compound 145 can be discharged into the bloodstream of the subject. The container 144 is configured to fit at least partially within the circumferential opening 142c' to allow sufficient movement of the projections 142b within the container 144 to expel the therapeutic compound 145 from the container 144. In this manner, the delivery structure 140 can deliver the therapeutic compound 145 into the GI lumen wall or into the surrounding tissue.

[0162] 11A shows a side cross-sectional view of a delivery structure 240 (an embodiment of the delivery structure 128) for use in one or more embodiments of the delivery assembly 120 of the present disclosure. The delivery structure 240 includes a holder 242, a container 244, a therapeutic compound 245 (an embodiment of the therapeutic compound 125) disposed within the container 244, and an actuation mechanism (e.g., a second actuator) including a piston 246. The actuation mechanism further includes an igniter 247, a charge 248, and an electrical circuit 260 (shown in block diagram form) for generating a force to move the piston 246. The delivery structure 240 is shown in a first state prior to reaching a desired location within the GI lumen for delivery of the therapeutic compound 245 within the GI lumen wall. As described below, the delivery structure 240 is a structure that actively delivers the therapeutic compound 245 from the container 244 to the GI lumen wall via the actuation mechanism. In one or more embodiments, the actuation mechanism of the delivery structure 240 can be of similar structure to the actuator 410 described above with reference to Figures 5A-5B.

[0163] For example, the holder 242 includes a peripheral wall 242a defining an open end 242d', a reaction chamber 242b, a piston chamber 242c, and an interior including a container portion 242d. The reaction chamber 242b is defined by a lower inner surface of the peripheral wall 242a. The piston chamber 242c is located above the reaction chamber 242b and configured to slidably receive the piston 246. The container portion 242d is located above the piston chamber 242c adjacent the open end 242d'. The reaction chamber 242b includes an igniter 247 and a charge 248 disposed therein. The charge 248 is located adjacent to and / or in contact with the igniter 247. The charge 248 may be a flammable material, such as nitrocellulose (e.g., a nitrocellulose sheet) or a composition of other flammable materials or combinations of materials. The igniter 247 may be a coil (as shown), a conductive wire or filament (e.g., a tungsten filament), or other structure for generating heat, a spark, a flame, or other energy sufficient to ignite the charge 248 in response to receiving an electric current. The holder 242 further includes electrical contacts 249 coupled to the peripheral wall 242a. The electrical contacts 249 are operably coupled to the igniter 247 and to an electrical circuit 260. In a first state, shown in FIG. 11A, a release mechanism 249′ (e.g., a second release means) in the form of a coating or cover is applied to each of the electrical contacts 249 at an outer portion of the holder 242 to temporarily prevent the electrical contacts 249 from contacting fluid in the GI tract. As described below, the electrical circuit 260 is configured to generate a signal (e.g., an electric current) in response to an electrical short occurring between the contacts 249 upon contact with bodily fluid in the GI tract when the release mechanism 249′ is activated (e.g., disassembled). The electrical circuit 260 is further configured to cause the igniter 247 to initiate combustion of the charge 248 in response to the generated signal.

[0164] The electrical circuit 260 may be similar in structure to the electrical circuit 419 described above with reference to FIGS. 5A-5B. For example, the electrical circuit 260 may include a power source (e.g., a battery) and one or more energy storage components (e.g., capacitors) coupled to the holder 242. The electrical circuit 260 may further include one or more additional electrical components. The electrical circuit 260 may be structured such that an electrical short across the contacts 249 causes current from the power source to be stored by the energy storage component. When a sufficient amount of current is stored in the energy storage component, the energy storage component may discharge the stored energy through the electrical circuit 260 and across the igniter 247, which then initiates the combustion of the charge 248.

[0165] Alternatively, the electrical circuitry 260 may include one or more sensors for sensing conditions within the GI tract and a processing circuit including a processor for executing instructions stored in a memory of the processing circuit in response to the sensed conditions to cause the igniter 247 to initiate combustion of the charge 248. For example, the one or more sensors may be coupled to the holder 242 and configured to sense conditions within the GI tract (e.g., pH value, temperature, electrolytic value) and generate a signal. The processor may receive the signal and discharge a current stored in an energy storage component based on information stored in the memory of the processing circuit, thereby causing activation of the igniter 247. For example, the information may include a threshold pH value, a range of pH values, a threshold temperature, a range of temperatures, or other information related to conditions within the GI tract.

[0166] The electrical circuit 260 may be configured to cause actuation of the igniter 247 at an appropriate time relative to actuation of the delivery assembly 120 by the actuator 110 to substantially preserve (e.g., from degradation) the therapeutic compound 245 for delivery to the GI luminal wall to achieve a desired therapeutic effect in the subject. For example, the electrical circuit 260 may include a timer that delays sending a signal to the igniter 247 for a sufficient time to allow the delivery assembly 120 to extend outside the GI luminal wall before the therapeutic compound 245 is expelled from the container 244 to the luminal wall. Alternatively, the electrical circuit 260 may include a capacitor configured to discharge a current to the igniter 247 after accumulating a certain amount of charge that can be related to the timing of actuation of the delivery assembly 120.

[0167] In embodiments that include electrical circuitry (e.g., electrical circuitry 419, 519) associated with the actuator 110 of the device, the electrical circuitry 260 may be omitted and the actuation mechanism (e.g., igniter 247) may instead be operably coupled to the electrical circuitry associated with the actuator 110. In these embodiments, the electrical circuitry associated with the actuator 110 may be structured to signal the igniter 247 at the appropriate time relative to actuation of the delivery assembly 120 to ensure delivery of the therapeutic compound 245 to the GI lumen wall after the delivery structure 240 is placed in contact with or adjacent to the GI lumen wall.

[0168] Still referring to FIG. 11A, piston 246 is slidably disposed within piston chamber 242c adjacent reaction chamber 242b. Piston 246 is slidably coupled to and can be sealably engaged (e.g., via one or more piston rings, seals) with an inner surface of peripheral wall 242a defining piston chamber 242c. Piston 246 includes shaft 246a that engages with an inner surface of piston chamber 242c and end 246b that extends from shaft 246a toward container portion 242d. End 246b has a tapered configuration (e.g., pointed) sufficient to penetrate a seal of container 244 coupled within container portion 242d. End 246b further has a configuration for contacting an engagement surface of therapeutic compound 245 to expel therapeutic compound 245 from container 244 into the GI lumen wall. As described below, in response to ignition of a charge 248 in reaction chamber 242b, piston 246 moves axially within piston chamber 242c toward reservoir portion 242d, expelling therapeutic compound 245 into the GI lumen wall.

[0169] The container 244 is coupled to the holder 242 at a fixed position within the container portion 242d. For example, the holder 242 can include one or more snap features, bayonet features, or other features for holding the container 244 within the container portion 242d. The container 244 is of the same structure as the container 144 described above, but is fixed relative to the holder 242 instead of being movable. As such, like reference numerals refer to like features between embodiments (e.g., body 144a is equivalent to body 244a). The container 244 is structured to contain the therapeutic compound 245 therein and to temporarily protect the therapeutic compound 245 from degradation in the GI tract. The container 244 is positioned relative to the holder 242 such that the second seal 244c is adjacent to the end 246b of the piston 246 and the first seal 244b is adjacent to the opening 242d'.

[0170] 11B, the delivery structure 240 is shown in a second state when the delivery structure 240 is moved adjacent to or into contact with the GI lumen wall (upon actuation of the actuator 110) via outward expansion of the delivery assembly 120. In the second state shown in FIG. 11B, bodily fluid within the GI lumen is permitted to reach the release mechanism 249' to actuate (e.g., degrade) the release mechanism 249'. In response to actuation of the release mechanism 249', bodily fluid within the GI tract creates an electrical short across the electrical contacts 249 such that current flows through the electrical circuit 260. The current generated in the electrical circuit 260 is sufficient to cause the igniter 247 to ignite the charge 248 to generate a combustion force within the reaction chamber 242b at the appropriate time relative to actuation of the delivery assembly 120 to ensure substantial preservation of the therapeutic formulation 245 for delivery to the GI lumen wall. For example, the timing of delivery of therapeutic compound 245 relative to actuation of delivery assembly 120 can be controlled by a number of factors, such as the structure of release mechanism 249' (e.g., rate of degradation), the structure of electrical circuit 260 (as discussed above), the structure of igniter 247, the structure / amount of charge 248, and / or the structure of piston 24 (e.g., amount of movement, resistance within piston chamber). Additionally or alternatively, actuation of release mechanism 249' can be controlled by temporarily blocking release mechanism 249' by a component of delivery assembly 120 (e.g., by one or more pivotable arms) such that movement / extension of delivery assembly 120 exposes release mechanism 249' to allow actuation of release mechanism 249'.

[0171] 11B, the force generated in reaction chamber 242b causes piston 246 to move within piston chamber 242c toward first seal 244b. This movement of piston 246 is sufficient to cause end 246b to penetrate first seal 244b and contact an engagement surface of therapeutic compound 245 (as indicated by unidirectional arrow 270), thereby expelling therapeutic compound 245 from container 244, through second seal 244c, and into the GI lumen wall or surrounding tissue, where one or more therapeutic agents of therapeutic compound 245 can subsequently be expelled into the bloodstream of the subject. In this manner, delivery structure 240 can actively deliver therapeutic compound 245 into the GI lumen wall or surrounding tissue.

[0172] 12A illustrates a side cross-sectional view of a delivery structure 340 (an embodiment of delivery structure 128) for use in one or more embodiments of a delivery assembly 120 in the present disclosure. The delivery structure 340 includes a holder 342, a container 344, a therapeutic formulation 345 (an embodiment of therapeutic formulation 125) disposed within the container 344, and an actuation mechanism (e.g., a second actuator) including a biasing member in the form of a piston 346 and a spring 347. The delivery structure 340 is shown in a first state prior to reaching a desired location within the GI lumen for delivery of the therapeutic formulation 345 into the GI lumen wall. As described below, the delivery structure 340 is a structure that actively delivers the therapeutic formulation 345 from the container 344 to the GI lumen wall by actuation of the spring 347.

[0173] The holder 342 includes a peripheral wall 342a defining an open end 342c' and an interior including a piston chamber 342b and a container portion 342c. The piston chamber 342b extends from a lower inner surface of the peripheral wall 342a to the container portion 342c. The piston chamber 342b is configured to slidably receive a piston 346 therein. The container portion 342c is located above the piston chamber 342b adjacent the open end 342c'. The spring 347 and the piston 346 are disposed within the piston chamber 342b such that in a first state shown in FIG. 12A, the spring 347 is held in compression between a lower inner surface of the peripheral wall 342a and a portion of the piston 346. The piston 346 can be slidably coupled to and sealably engaged (e.g., via one or more piston rings, seals) with an inner surface of the peripheral wall 342a defining the piston chamber 342b.

[0174] For example, piston 346 includes shaft 346a and piston portion 346b extending from shaft 346a. Piston portion 346b movably engages an inner surface of piston chamber 342b. Piston portion 346b further includes a tapered (e.g., pointed) end 346b' for penetrating the seal of container 344 and engaging an engagement surface of therapeutic formulation 345. Shaft 346a is shown disposed in opening 342d of peripheral wall 342a through spring 347 such that spring 347 contacts an underside of piston portion 346b. A release mechanism 348 (e.g., a second release) is coupled to shaft 346a at opening 342d to temporarily hold piston 346 in position relative to holder 342, thereby compressing spring 347 in a first state shown in FIG. 12A. The release mechanism 348 may be constructed from a degradable material that degrades in response to contact with fluid within the GI tract to cause release of the piston 346. Additionally or alternatively, the release mechanism 348 may be configured as a latch, clip, or other structure that can release the piston 346 in response to conditions (e.g., temperature, pH value) within the GI tract; as described below, the spring 347 is a structure that expands in response to actuation of the release mechanism 348 to move the piston 346 towards the reservoir 344 to deliver the therapeutic formulation 345 into the GI lumen wall.

[0175] The container 344 is coupled to the holder 342 at a fixed position within the container portion 342c. For example, the holder 342 can include one or more snap features, bayonet features, or other features for holding the container 344 within the container portion 342c. The container 344 is of the same structure as the container 244 described above. As such, like reference numerals refer to like features between embodiments (e.g., body 244a is equivalent to body 344a). The container 344 is structured to contain the therapeutic compound 345 therein and to temporarily protect the therapeutic compound 345 from degradation in the GI tract. The container 344 is positioned relative to the holder 342 such that the second seal 344c is adjacent to the end 346b of the piston 346 and the first seal 344b is adjacent to the opening 342c'.

[0176] 12B, the delivery structure 340 is shown in a second state when the delivery structure 340 is moved adjacent to or into contact with the GI lumen wall (upon actuation of the actuator 110) via outward extension of the delivery assembly 120. In the second state shown in FIG. 12B, fluid within the GI lumen is permitted to reach the release mechanism 348 to actuate (e.g., disassemble and / or release) the release mechanism 348. In response to actuation of the release mechanism 348, the biasing force of the spring 347 overcomes the retention force of the piston 346 by the release mechanism 348, allowing the spring 347 to expand and move the piston 346 within the piston chamber 342b toward the container 344. This movement of piston 346 is sufficient to cause end 346b' to penetrate first seal 344b and contact the engagement surface of therapeutic compound 345 (as indicated by unidirectional arrow 370), thereby expelling therapeutic compound 345 from container 344, through second seal 344c and into the GI lumen wall or surrounding tissue, where one or more therapeutic agents of therapeutic compound 345 can be expelled into the subject's bloodstream.

[0177] Actuation of the spring 347 can be appropriately timed relative to actuation of the delivery assembly 120 to ensure substantial preservation of the therapeutic formulation 345 for delivery to the GI lumen wall. For example, the timing of delivery of the therapeutic formulation 345 relative to actuation of the delivery assembly 120 can be controlled by a number of factors, such as the configuration of the release mechanism 348 (e.g., degradation rate), the configuration of the spring 347 (e.g., spring constant, spring size, spring length), and the configuration of the piston 346 or piston chamber 342b (e.g., amount of piston travel, resistance within the piston chamber). Additionally or alternatively, actuation of the release mechanism 248 can be controlled by temporarily blocking the release mechanism 248 by a component of the device 100 (e.g., by one or more pivotable arms) such that movement / extension of the delivery assembly 120 exposes and / or moves the release mechanism 248 to allow actuation of the release mechanism 248.

[0178] 13A shows a side cross-sectional view of a delivery structure 440 (an embodiment of the delivery structure 128) for use in one or more embodiments of the delivery assembly 120 in the present disclosure. The delivery structure 440 includes a holder 442, a container 444, a therapeutic formulation 445 (an embodiment of the therapeutic formulation 125) disposed within the container 444, and an actuation mechanism (e.g., a second actuator) including a piston 446. The actuation mechanism further includes a first reactant 449a and a second reactant 449b disposed within respective chambers of the holder 442 to be mixed together to generate a gas for moving the piston 446. The delivery structure 440 is shown in a first state prior to reaching a desired location within the GI lumen for delivery of the therapeutic formulation 445 within the GI lumen wall. As described below, the delivery structure 440 is a structure that actively delivers the therapeutic formulation 445 from the container 444 to the GI lumen wall by the actuation mechanism.

[0179] The holder 442 includes a peripheral wall 442a defining an open end 442d', a reaction chamber 442b, a piston chamber 442c, and an interior including a container portion 442d. The reaction chamber 442b is defined by a lower inner surface of the peripheral wall 442a and includes a first reactant 449a (e.g., potassium bicarbonate) disposed therein. The piston chamber 442c is located above the reaction chamber 442b and is configured to slidably receive a piston 446. The piston 446 includes a piston portion 446a that slidably engages with an inner surface of the peripheral wall 442a that defines the piston chamber 442c. The piston 446 further includes a tapered (e.g., pointed) end 446a for penetrating a seal of the container 444 and engaging an engagement surface of the therapeutic formulation 445.

[0180] The piston chamber 442c further includes a second reactant 449b (e.g., citric acid) disposed below the piston 446 adjacent the reaction chamber 442b. The container portion 442d is disposed above the piston chamber 442c adjacent the open end 442d'. The reaction chamber 442b is fluidly coupled to the piston chamber 442c by a conduit 448. However, in a first state shown in FIG. 12A, the conduit 448 includes a release mechanism 447 (e.g., a second release means) coupled thereto for temporarily blocking the flow of fluid between the reaction chamber 442b and the piston chamber 442c. For example, the conduit 448 may be a flexible tube (e.g., a silicone tube), and the release mechanism 447 may be a clip, a latch, or other structure that functions as a pinch valve to temporarily block the flow of fluid through the conduit 448. The release mechanism 447 may be constructed of a degradable material that degrades in response to contact with fluid in the GI tract. Additionally or alternatively, the release mechanism 447 can be structured as a latch, clip, or other structure that can move or otherwise release from the conduit 448. Alternatively, the release mechanism 447 may be configured as another type of valve member that is movable relative to the holder 442 to selectively fluidly connect the reaction chamber 442b and the piston chamber 442c in response to conditions in the GI tract and / or movement of components of the device 100 (e.g., pivotable movement of one or more arms). The holder 442 further includes one or more openings 450 for providing a fluid path from the GI lumen environment to the release mechanism 447. As described below, the release mechanism 447 is configured to release the conduit 448 to allow the first reactant 449a to flow from the reaction chamber 442b to the piston chamber 442c, where the first reactant 449a mixes with the second reactant 449b to generate a gas (e.g., CO2) having sufficient pressure to move the piston 446 toward the container 444.

[0181] The container 444 is coupled to the holder 442 at a fixed position within the container portion 442d. For example, the holder 442 can include one or more snap features, bayonet features, or other features for holding the container 444 within the container portion 442d. The container 444 is of the same structure as the container 244 described above. As such, like reference numerals refer to like features between embodiments (e.g., body 244a is equivalent to body 444a). The container 444 is structured to contain one or more therapeutic compounds 445 therein and to temporarily protect the therapeutic compounds 445 from degradation in the GI tract. The container 444 is positioned relative to the holder 442 such that the second seal 444c is adjacent to the end 446b of the piston 446 and the first seal 444b is adjacent to the opening 442d'.

[0182] 13B, the delivery structure 440 is shown in a second state when the delivery structure 440 is moved adjacent to or into contact with the GI lumen wall (upon actuation of the actuator 110) via outward expansion of the delivery assembly 120. In the second state shown in FIG. 13B, fluid within the GI lumen is permitted to reach the release mechanism 447 to actuate (e.g., disintegrate and / or release) the release mechanism 447. In response to actuation of the release mechanism 447, the conduit 448 is at least partially or fully opened such that the first reactant 449a has sufficient pressure to flow from the reaction chamber 442b into the piston chamber 442c and mix with the second reactant 449b to generate gas (e.g., CO2), which moves the piston 446 within the piston chamber 445 towards the container 444. This movement of piston 446 is sufficient to cause end 446b to penetrate first seal 444b and contact the mating surface of therapeutic compound 445, thereby expelling therapeutic compound 445 from container 444, through second seal 444c (as indicated by unidirectional arrow 460) and into the GI lumen wall or surrounding tissue, where one or more therapeutic agents of therapeutic compound 445 can then be expelled into the subject's bloodstream.

[0183] Delivery of the therapeutic compound 445 from the container 444 can be appropriately timed relative to actuation of the delivery assembly 120 to ensure substantial preservation of the therapeutic compound 445 for delivery to the GI lumen wall. For example, the timing of delivery of the therapeutic compound 445 relative to actuation of the delivery assembly 120 can be controlled by a number of factors, such as the configuration of the release mechanism 447 (e.g., degradation rate), the configuration of the conduit 448 (e.g., length, inner diameter), the amount or type of reactants 449a, 449b, and the configuration of the piston 446 or piston chamber 442c (e.g., amount of piston movement, resistance within piston chamber). Additionally or alternatively, actuation of the release mechanism 447 can be controlled by temporarily blocking the release mechanism 447 by a component of the device 100 (e.g., one or more pivotable arms) such that movement / extension of the delivery assembly 120 exposes and / or moves the release mechanism 447 to allow actuation of the release mechanism 447.

[0184] FIG. 14A shows a front cross-sectional view of an ingestible device 900 (one embodiment of ingestible device 100) positioned within the lumen of a subject's GI tract after being ingested. The ingestible device 900 is shown in a first state prior to reaching a desired location within the GI lumen for delivery of a therapeutic formulation into the GI lumen wall. As shown in the front view of FIG. 14A, the ingestible device 900 includes a housing 902 (an embodiment of housing 102), a support 915 (an embodiment of support 115) disposed within the housing 902, and a plurality of delivery assemblies 920 (an embodiment of delivery assembly 120) coupled to and circumferentially disposed around the support 915. Although the support 915 is shown as having a circular cross-sectional shape, it should be understood that the support 915 may have any suitable cross-sectional shape (e.g., ellipsoid, triangle, square, pentagon, hexagon). Although ingestible device 900 is shown including four delivery assemblies 920, ingestible device 900 may include more or less than four delivery assemblies 920 according to other embodiments. Delivery assemblies 920 are positioned equidistant from one another, but may be spaced at different intervals according to other embodiments. Each of delivery assemblies 920 includes a delivery structure 928 (an embodiment of delivery structure 128) that includes therein one or more therapeutic formulations 925 (an embodiment of therapeutic formulation 125) for delivery into the GI lumen wall.

[0185] 14B, the ingestible device 900 is shown in a second state upon reaching a desired location in the GI tract, in this example the small intestine, for delivery of the therapeutic formulation 925 from the delivery structure 928 to the intestinal wall. As shown in FIG. 14B, the housing 902 is at least partially (or completely) degraded as a result of the ingestible device 900 reaching the small intestine, which may be associated, for example, with a selected or threshold pH value associated with the small intestine to trigger the degradation of the housing 902. As a result of the at least partial degradation of the housing 902, fluid within the small intestine is permitted to reach the interior of the housing 902 and contact a release means (not shown) associated with an actuator (not shown) of the device to actuate (e.g., degrade) the release means. In response to actuation of the release means, the actuator extends the delivery assembly 920 outwardly from the support 915 toward the intestinal wall so that the delivery structure 928 can deliver the therapeutic compound 925 into the intestinal wall or into the surrounding tissue (e.g., the peritoneum or peritoneal cavity), and one or more therapeutic agents of the therapeutic compound 925 can subsequently be discharged into the subject's bloodstream.

[0186] 15, a method 1000 of delivering a therapeutic formulation 125 into the GI lumen wall or surrounding tissue of a subject using an ingestible device 100 is diagrammatically shown. In a first step 1001, the ingestible device 100 is orally administered to a subject by swallowing the ingestible device 100. In a second step 1002, the housing 102 and / or the outer coating 104 are at least partially (or completely) degraded as a result of the ingestible device 100 reaching a desired location in the GI tract (e.g., stomach, small intestine) of the subject, which is associated with, for example, a selected or threshold pH value for triggering the degradation of the housing 102. In a third step 1003, fluid in the GI tract is allowed to reach the interior of the housing 102 to contact the release means 108, so as to activate the release means 108 and trigger the actuator 110. In a fourth step 1004, the actuator 110 axially extends the stretcher 130 along a longitudinal axis defined by the support 115 to substantially align the longitudinal axis with the longitudinal axis of the GI lumen. In a fifth step 1005, the actuator 110 further pivots the one or more arms such that the delivery assembly 120 extends outwardly away from the support 115 toward the GI lumen wall. In one or more embodiments, step 1005 is performed substantially simultaneously with step 1004. In other embodiments, step 1005 is performed after step 1004. In a sixth step 1006, the delivery structure 128 expels the therapeutic formulation 125 into the GI lumen wall or into the surrounding tissue (e.g., with the delivery structure 140) without a separate actuation mechanism in response to the delivery structure 128 contacting the GI lumen wall as the delivery assembly 120 is extended outwardly. Additionally or alternatively, the delivery structure 128 actively expels the therapeutic compound 125 (e.g., using delivery structures 240, 340, 440) into the GI luminal wall or surrounding tissue in response to separate release and actuation mechanisms associated with the delivery structure 128. The therapeutic compound 125 can then degrade at the luminal wall or surrounding tissue to expel one or more therapeutic agents into the subject's bloodstream to provide a desired therapeutic effect.

[0187] The foregoing description of various embodiments has been presented for purposes of illustration and description. It is not intended to limit the invention to the precise form disclosed. Many modifications, variations, and improvements will be apparent to those skilled in the art. For example, device embodiments can be sized and otherwise adapted for various pediatric and neonatal applications, as well as various veterinary applications. Additionally, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific devices and methods described herein. Such equivalents are deemed to be within the scope of the present disclosure.

[0188] Although the present disclosure has been described and illustrated with reference to specific embodiments thereof, these descriptions and illustrations are not intended to limit the present disclosure. It can be clearly understood that various changes can be made within the embodiments and equivalent components can be substituted without departing from the true spirit and scope of the present disclosure as defined by the appended claims. Also, components, properties, or acts from one embodiment can be easily recombined or substituted with one or more components, properties, or acts from other embodiments to form numerous additional embodiments within the scope of the present invention. Moreover, a component illustrated or described as being combined with other components can exist as a single component in various embodiments. Furthermore, when a component, property, component, feature, step, etc. is actively described, the embodiment of the present invention specifically contemplates the exclusion of that component, value, property, component, feature, step, etc. The illustrations are not necessarily drawn to scale. There can be a distinction between the artistic depictions in the present disclosure and the actual device due to variables in the manufacturing process, etc. There can be other embodiments of the present disclosure that are not specifically illustrated. The present specification and drawings are considered to be illustrative and not restrictive. Modifications may be made to adapt a particular situation, material, composition of matter, method, or process to the objective, spirit, and scope of the present disclosure. All such modifications are intended to be within the scope of the claims appended hereto. Although the methods disclosed herein have been described with reference to certain operations performed in a particular order, it will be understood that these operations can be combined, sub-divided, or re-sequenced to form equivalent methods without departing from the teachings of the present disclosure. Thus, unless specifically indicated herein, the order and grouping of operations are not limitations of the present disclosure.

Claims

1. An ingestible device for delivering a therapeutic formulation into the luminal wall or surrounding tissue of the gastrointestinal tract (GI duct) of a subject, The casing and A support structure is placed inside the housing and defines the longitudinal axis, An arm pivotably coupled to the support, The support is connected via the arm, A delivery assembly comprising a delivery structure coupled to the arm, and the therapeutic formulation disposed on the delivery structure, A stretcher, which is attached to the support and configured to extend along the longitudinal axis so as to substantially align the delivery structure with respect to the lumen wall, The actuator is coupled to the arm, The system comprises a release means coupled to the actuator and configured to operate in response to the state inside the GI pipe in order to operate the actuator, The actuator, the support, the delivery assembly, the arm, and the extender are each housed inside the housing. In response to the operation of the release means, the actuator extends the extender along the longitudinal axis and pivots the arm relative to the support so that the delivery assembly extends outward from the longitudinal axis toward the lumen wall and delivers the therapeutic formulation from the delivery structure into the lumen wall or the surrounding tissue. device.

2. The device according to claim 1, wherein the actuator is configured to generate an axial force along the longitudinal axis to pivot the arm.

3. The device according to claim 1, wherein the actuator is configured to generate a rotational force about the longitudinal axis to pivot the arm.

4. The device according to any one of claims 1 to 3, wherein the support comprises a plurality of sections movably coupled to define an expandable configuration, and when the release means is activated, the plurality of sections move relative to each other so that the support extends axially along the longitudinal axis.

5. The device according to any one of claims 1 to 3, wherein the actuator is further coupled to the stretcher, and when the release means is actuated, the actuator substantially simultaneously stretches the delivery assembly outward away from the longitudinal axis and stretches the stretcher along the longitudinal axis.

6. The device according to any one of claims 1 to 3, wherein the housing is configured as a capsule including a first segment and a second segment, and the first segment is detachably coupled to the second segment.

7. The device according to claim 6, wherein at least one of the actuator, the support, or the expander has a structure that spreads the first and second segments apart.

8. The device according to any one of claims 1 to 3, wherein the delivery structure includes a holder coupled to the arm and a container coupled to the holder, and the therapeutic preparation is disposed in the container.

9. The device according to claim 8, wherein the holder defines a piston chamber, and the delivery structure includes a piston slidably disposed within the piston chamber.

10. The device according to claim 9, wherein the delivery structure further includes a spring coupled to the piston and a release mechanism coupled to the spring, and when the release mechanism is activated, the spring expands to cause the piston to discharge the therapeutic preparation from the container into the lumen wall.

11. The device according to any one of claims 1 to 3, wherein the delivery structure includes a holding feature for temporarily holding the delivery structure with respect to the lumen wall.

12. The device according to any one of claims 1 to 3, further comprising a plurality of arms pivotably connected to one another in a cross shape to define a scissor mechanism, wherein the arm is one of the plurality of arms.

13. The device according to any one of claims 1 to 3, wherein the actuator includes a spring, the spring is held in a compressed state by the release means, and when the release means is operated, the spring expands along the longitudinal axis to pivot the arm relative to the support.

14. The device according to any one of claims 1 to 3, wherein the actuator includes an inflatable member configured to function as an expander, the inflatable member includes a plurality of reactants disposed therein, the plurality of reactants are temporarily separated from each other by a release means, the release means is coupled to the inflatable member, and when the release means is activated, the plurality of reactants mix and undergo a chemical reaction within the inflatable member, generating a gas that expands the inflatable member, thereby pivoting the arm relative to the support.

15. The device according to any one of claims 1 to 3, wherein the actuator includes a housing defining a piston chamber, and the support includes a piston slidably disposed within the piston chamber.

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