Devices, assemblies and methods for delivering fluid formulations inside the gastrointestinal tract - Patents.com

Abstract

A delivery assembly (110) for an ingestible device for delivering a fluid formulation into a GI tract lumen wall or surrounding tissue of a subject includes a housing (112, 302), a piston-and-needle assembly (120, 320), a membrane (114, 315), and a valve member (118). The housing defines a chamber. The piston-and-needle assembly is movably disposed within the chamber and includes an inlet (326b') and a channel (324b'). The membrane (114, 315) is coupled to the housing such that the membrane (114, 315) and the housing (112, 302) cooperate to define a reservoir (315a) for containing the fluid formulation. The housing (12, 302) further defines an opening (302a') extending between the chamber and the reservoir (315a). When the piston-needle assembly (120, 320) is sufficiently moved relative to the housing (112, 302), the valve member (118) opens and the fluid formulation flows from the reservoir (315a) through the opening (302a') and into the chamber, where it is directed to the inlet (326b') and flow path (324b') for delivery into the Gl lumen wall or 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 / 312,355, filed February 21, 2022, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] Therapeutic agents, such as drugs, can be administered to subjects (patients) by ingestion or parenteral injection (e.g., subcutaneously, intramuscularly, or intravenously) to provide a desired therapeutic effect. However, these routes of administration have several drawbacks. For example, some therapeutic agents, such as molecules with large molecular weights (macromolecules), 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 may experience pain and inconvenience that significantly impact compliance and quality of life.

[0003] To address these shortcomings, ingestible devices have been proposed for orally administering solid dosage therapeutic agents to the luminal wall or surrounding tissue of the GI tract.However, solid dosage forms may be limited to relatively small dosage amounts (e.g., a few milligrams).Therefore, the use of solid dosage forms may be disadvantageous for treatment regimens that require higher dosage amounts, for example, for reasons of administration frequency, convenience, or cost.

[0004] Thus, there is a need for devices that can deliver a wide range of dosages of therapeutic agents and that can address one or more of the shortcomings associated with traditional oral and parenteral administration routes. Summary of the Invention [Problem to be solved by the invention]

[0005] Embodiments of the present disclosure generally relate to devices, assemblies, and methods for delivering a fluid formulation to the GI tract (e.g., the GI luminal wall or surrounding tissue) of a subject. The devices and assemblies are configured to deliver up to about 400 microliters (μL) or more of a fluid formulation, which may include up to about 100 milligrams (mg) or more of at least one therapeutic agent. In this manner, the disclosed devices, assemblies, and methods can enable efficient delivery of a wide range of dosages of a therapeutic agent for most treatment regimens. [Means for solving the problem]

[0006] In one aspect, a delivery assembly for an ingestible device for delivering a fluid formulation to a GI luminal wall or surrounding tissue of a subject includes a housing, a piston-needle assembly, a membrane, and a valve member. The housing defines a chamber. The piston-needle assembly is movably disposed within the chamber and includes an inlet and a channel. The membrane is coupled to the housing such that the membrane and the housing cooperate to define a reservoir for containing the fluid formulation. The housing further defines an opening extending between the chamber and the reservoir. The valve member selectively controls flow of the fluid formulation from the reservoir through the opening to the chamber. In response to sufficient movement of the piston-needle assembly relative to the housing, the valve member opens to allow the fluid formulation to flow from the reservoir through the opening to the chamber. The fluid formulation is directed from the chamber to the inlet and the channel for delivery into the GI luminal wall or surrounding tissue.

[0007] In another aspect, an ingestible device for delivering a fluid formulation to a GI luminal wall or surrounding tissue of a subject includes an expandable member and a delivery assembly coupled to and disposed within the expandable member. The delivery assembly includes a housing, a piston-needle assembly, a membrane, a fluid formulation, and a valve member. The housing defines a chamber. The piston-needle assembly is movably disposed within the chamber and includes an inlet and a channel. The membrane is coupled to the housing such that the membrane and the housing cooperate to define a reservoir. The housing further defines an opening extending between the chamber and the reservoir. The fluid formulation is disposed within the reservoir and includes at least one therapeutic agent. The valve member selectively controls flow of the fluid formulation from the reservoir through the opening to the chamber. In response to sufficient movement of the piston-needle assembly relative to the housing, the valve member opens to allow the fluid formulation to flow from the reservoir through the opening to the chamber. The fluid formulation is directed from the chamber to the inlet and the channel for delivery into the GI luminal wall or surrounding tissue.

[0008] In another aspect, a method for delivering a fluid formulation into a GI luminal wall or surrounding tissue of a subject in need thereof includes ingesting an ingestible device as described herein by the subject. The ingestible device includes an expandable member and a delivery assembly coupled to and disposed within the expandable member. The delivery assembly includes a housing, a piston-needle assembly, a membrane, a fluid formulation, and a valve member. The housing defines a chamber. The piston-needle assembly is movably disposed within the chamber and includes an inlet and a channel. The membrane is coupled to the housing such that the membrane and the housing cooperate to define a reservoir. The housing further defines an opening extending between the chamber and the reservoir. The fluid formulation is disposed within the reservoir and includes at least one therapeutic agent. The valve member selectively controls flow of the fluid formulation from the reservoir through the opening to the chamber. In response to sufficient movement of the piston-needle assembly relative to the housing, the valve member opens to allow the fluid formulation to flow from the reservoir through the opening to the chamber. The fluid formulation is directed from the chamber to the inlet and channel for delivery into the GI lumen wall or to the surrounding tissue.

[0009] In another aspect, use of an ingestible device to deliver a fluid formulation into a GI luminal wall or surrounding tissue of a subject in need thereof includes ingesting an ingestible device as described herein by the subject. The ingestible device includes an expandable member and a delivery assembly coupled to and disposed within the expandable member. The delivery assembly includes a housing, a piston-needle assembly, a membrane, a fluid formulation, and a valve member. The housing defines a chamber. The piston-needle assembly is movably disposed within the chamber and includes an inlet and a channel. The membrane is coupled to the housing such that the membrane and the housing cooperate to define a reservoir. The housing further defines an opening extending between the chamber and the reservoir. The fluid formulation is disposed within the reservoir and includes at least one therapeutic agent. The valve member selectively controls flow of the fluid formulation from the reservoir through the opening to the chamber. In response to sufficient movement of the piston-needle assembly relative to the housing, the valve member opens to allow the fluid formulation to flow from the reservoir through the opening to the chamber. The fluid formulation is directed from the chamber to the inlet and into the channel for delivery into the GI lumen wall or into the surrounding tissue.

[0010] In another aspect, a method of preparing an ingestible device for delivering a therapeutic agent into the GI tract lumen wall or surrounding tissue of a subject is provided, the method comprising loading a fluid formulation comprising a therapeutic agent into a delivery assembly described herein.

[0011] In one or more embodiments of any of the aforementioned aspects, the piston-needle assembly and the housing cooperatively define a fluid channel in the chamber for directing the fluid formulation from the opening to the inlet.

[0012] In one or more embodiments of any of the aforementioned aspects, the valve member includes a plug removably coupled to the housing at the opening. In one or more embodiments, the piston-needle assembly engages the plug to disengage the plug from the housing and allow the fluid formulation to flow from the reservoir through the opening and into the chamber.

[0013] In one or more embodiments of any of the preceding aspects, the valve member includes a piercing member and a seal, the seal coupled to the housing at the opening. In one or more embodiments, the piston-needle assembly engages the piercing member to pierce the seal and allow the fluid formulation to flow from the reservoir through the opening and into the chamber. In one or more embodiments, the piercing member is configured as a flexible tab having a tapered end. In one or more embodiments, the piercing member is configured as an elongated shaft having a tapered end.

[0014] In one or more embodiments of any of the aforementioned aspects, the device further comprises an ingestible housing for delivery to the GI tract of a subject.

[0015] In one or more embodiments of any of the aforementioned aspects, the expandable member comprises a balloon.

[0016] In one or more embodiments of any of the preceding aspects, the device further includes a plurality of reactants disposed within the balloon to generate gas pressure within the balloon to expand the balloon within the GI lumen.

[0017] In one or more embodiments of any of the aforementioned aspects, the piston-needle assembly is configured to move relative to the housing in response to gas pressure applied against a surface of the piston-needle assembly to advance a portion of the piston-needle assembly into the GI lumen wall or into surrounding tissue.

[0018] In one or more embodiments of any of the aforementioned aspects, the membrane comprises a flexible material to allow deformation of the membrane by gas pressure applied to an outer surface of the membrane to expel the fluid formulation from the reservoir into the chamber.

[0019] In one or more embodiments of any of the aforementioned aspects, the piston-needle assembly is configured to penetrate through the GI luminal wall and into the peritoneum or peritoneal cavity of the subject to expel the fluid formulation therein.

[0020] In one or more embodiments of any of the aforementioned aspects, the reservoir defines a volume containing up to about 400 μL of fluid.

[0021] In one or more embodiments of any of the aforementioned aspects, the reservoir defines a volume containing between about 50 μL and about 300 μL of fluid.

[0022] In one or more embodiments of any of the aforementioned aspects, the delivery assembly further includes a cover coupled to the housing, the cover defining a release mechanism for temporarily holding the piston-needle assembly in an axial position relative to the housing.

[0023] In one or more embodiments of any of the aforementioned aspects, the cover includes a first cover portion coupled to the housing and a second cover portion coupled to the piston-needle assembly, and the release mechanism is defined by one or more tabs releasably coupled between the first cover portion and the second cover portion.

[0024] In one or more embodiments of any of the preceding aspects, the cover further includes one or more openings to allow gas pressure to be applied against a surface of the piston-needle assembly, and the one or more tabs are configured to disengage from at least one of the first cover portion or the second cover portion to allow the piston-needle assembly to move axially relative to the housing in response to the gas pressure reaching a threshold value.

[0025] In one or more embodiments of any of the aforementioned aspects, the membrane extends circumferentially about the housing.

[0026] In one or more embodiments of any of the aforementioned aspects, the housing includes one or more fill ports for filling the reservoir with the fluid formulation.

[0027] In one or more embodiments of any of the aforementioned aspects, the delivery assembly further includes a fluid formulation disposed in the reservoir, the fluid formulation including at least one therapeutic agent.

[0028] In one or more embodiments of any of the preceding aspects, the at least one therapeutic agent is one or more selected from an immunosuppressant, a chemotherapeutic agent, a central nervous system (CNS) drug, an antidiabetic drug, an enzyme replacement therapy (ERT) drug, an antibody, a hormone, insulin, an incretin, or a combination thereof, or an oligonucleotide.

[0029] 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]

[0030] [Figure 1] FIG. 1 is a block diagram illustrating one embodiment of a device for delivering a fluid formulation into the GI tract of a subject. [Diagram 2] FIG. 2 is a cross-sectional view of one embodiment of the device of FIG. [Diagram 3] FIG. 3 is a detailed view of a portion of the device of FIG. 2 including a delivery assembly. [Figure 4] FIG. 4 is a partial perspective view of the delivery assembly of FIG. 3 without the membrane. [Diagram 5] FIG. 5 is another partial perspective view of the delivery assembly of FIG. 3 without the membrane. [Figure 6] FIG. 6 shows the device of FIG. 3 in a second state when it has reached a desired location within the GI tract for delivering a fluid formulation. [Figure 7] FIG. 7 is a perspective view of a valve member in the form of a piercing member according to an exemplary embodiment. [Figure 8] 8 is a partial cross-sectional view of the device of FIG. 2 with the penetrating member of FIG. [Figure 9] FIG. 9 shows the device of FIG. 2 with a valve member in the form of a plug according to another exemplary embodiment. [Figure 10] FIG. 10 shows the device of FIG. 2 with a valve member in the form of a plug according to another exemplary embodiment. [Figure 11] FIG. 11 illustrates a method of delivering a fluid formulation to the GI tract of a subject using the devices and assemblies of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] Before describing the details of the devices, assemblies, and methods of the present disclosure, some conventions are presented for the convenience of the reader.

[0032] 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.

[0033] 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."

[0034] 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).

[0035] 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).

[0036] 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.

[0037] 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.

[0038] 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.

[0039] As used herein, the term "body" refers to an animal body, unless the context clearly indicates otherwise.

[0040] 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., bovine, canine, feline, equine, or human). In certain embodiments, the subject, individual, or patient is a human.

[0041] 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.

[0042] 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).

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] Referring generally to the drawings, disclosed herein are embodiments relating to devices, assemblies, and methods for delivering a fluid formulation to the luminal wall of the GI tract or surrounding tissue (e.g., the peritoneum or peritoneal cavity) of a subject. The devices are advantageously configured to substantially preserve one or more therapeutic agents in the fluid formulation within the GI lumen for delivery within the GI lumen wall or surrounding tissue. Delivery to the lumen wall or surrounding tissue may allow for systemic uptake of one or more therapeutic agents in the fluid formulation. Additionally, the fluid form of the formulation may allow for the delivery of a wide range of dosages (e.g., up to about 100 mg or more) of one or more therapeutic agents for most treatment regimens. As described below, the disclosed devices and assemblies can deliver a variety of different types of therapeutic agents, such as macromolecules that are not typically suitable for delivery via ingestion. In this manner, the disclosed devices, assemblies, and methods can address many of the shortcomings associated with traditional oral and parenteral routes of administration.

[0052] 1 illustrates in block diagram form an example of a device 100 in accordance with one or more embodiments of the present disclosure. The device 100 includes an enclosure 102, an optional outer coating 104, an expandable member 106, a release 108, and a delivery assembly 110. The delivery assembly 110 includes a housing 112, a membrane 114, a fluid formulation 116, a valve member 118, and a piston-needle assembly 120.

[0053] According to a non-limiting example, 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 (e.g., stomach or small intestine) for delivery of the fluid formulation 116, 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 is actuated to cause a chemical reaction within the expandable member 106 that results in the formation of a gas to inflate the expandable member 106, as described in more detail below. Expansion of the expandable member 106 within the GI lumen places the delivery assembly 110 in close proximity (e.g., adjacent or in contact with) the lumen wall. When an internal pressure created by the gas within the expandable member 106 reaches a threshold value (e.g., upon expansion of the expandable member 106), the gas pressure causes the piston-needle assembly 120 to move relative to the housing 112, advancing a portion of the piston-needle assembly 120 into the GI lumen wall. The internal pressure created by the gas is also applied against the exterior surface of the membrane 114 before the fluid formulation 116 is discharged into a chamber of the housing 112 for subsequent delivery into the GI lumen wall. In response to sufficient movement of the piston-needle assembly 120 (e.g., sufficient penetration into the GI lumen wall), the valve member 118 opens, allowing the fluid formulation 116 to flow from a reservoir defined by the membrane 114 and the housing 112 into the chamber where it can flow through the piston-needle assembly 120 and into the GI lumen wall or into the surrounding tissue.

[0054] The housing 102 and optional outer coating 104, if provided, are configured to allow ingestion of the device 100 and temporarily protect the contents of the device 100 from degradation within one or more portions of the GI tract of a subject. The housing 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 of the components of the device 100 (e.g., at least the member 106, the release means 108, and the delivery assembly 110, as described below). In one or more embodiments, the housing 102 includes two or more sections that are coupled (e.g., press-fit) together to define the housing 102. For example, the housing 102 may be configured as a capsule that includes a first portion that at least partially overlaps a second portion in a press-fit arrangement to define the housing 102. The first and second portions may be releasably coupled to allow separation of the two portions. In one or more embodiments, the expandable member 106, the release means 108, and the delivery assembly 110 are each configured to be housed 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.

[0055] In one or more embodiments, the housing 102 can degrade under certain conditions. Additionally, different portions of the housing 102 can be configured to degrade under different conditions or at different degradation rates depending on the target site in the GI tract for delivery of the fluid formulation 116. For example, some or all of the housing 102 may be constructed of a material that degrades in water (e.g., in the presence of water in the form of humidity or moisture in the surrounding environment, such as within the body) and / or when exposed to a pH level above a certain threshold or within a certain range (e.g., a pH level associated with a target site in the GI tract for delivery of the fluid formulation 116).

[0056] An optional outer coating 104 optionally covers some or all of the housing 102. The outer coating 104 may include a single layer or multiple layers. The various layers may be formed of the same material or a combination of different materials. In one or more embodiments, the outer coating 104 may degrade under certain conditions, as described above with reference to the housing 102. One example of an outer coating 104 is an enteric coating, such as an enteric coating that degrades at a predetermined rate in water and / or an enteric coating that degrades when exposed to a solution having a pH level above a certain threshold or within a certain range. Another example of an outer coating 104 is a protective coating (e.g., a wax), such as a coating that protects a portion of the outer surface of the housing 102 from contact with fluids or tissues (e.g., bodily tissues or fluids).

[0057] In one or more embodiments, degradation of the housing 102 and / or outer coating 104 allows 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 may be located on an exterior portion of the housing 102, and degradation of the outer coating 104 may expose the release means 108 to a surface of the housing 102 to facilitate activation of the release means 108. Alternatively, the release means 108 may be located in a portion of the housing 102 that is not exposed to the outer coating 104, and the release means 108 may be structured to degrade at a different rate than the housing 102 and / or under different conditions within the GI tract.

[0058] The housing 102 and / or the outer coating 104 may define one or more degradation regions for localized degradation of the housing 102 and / or the outer coating 104, for example, to enable controlled degradation and detachment of the housing 102. For example, the outer coating 104 may 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 faster than other regions of the housing 102. This controlled degradation of the housing 102 allows for more consistent detachment of the housing 102 to enable delivery of the fluid formulation 116 from the delivery assembly 110 into the GI lumen wall.

[0059] The expandable member 106 is a flexible, adjustable structure. In one or more embodiments, the expandable member 106 is configured to expand from a collapsed state (e.g., folded, rolled, flattened) to an expanded state within a desired location of the GI lumen for delivery of the fluid formulation 116. The expandable member 106 may have a variety of different shapes, sizes, and configurations for temporary storage in the housing 102 and deployment within the lumen of the subject's GI tract. The expandable member 106 may be configured as a balloon, a bellows / accordion structure, or any other structure that is adjustable from a collapsed state to an expanded state.

[0060] The expandable member 106 defines an interior volume for containing various components of the device 100. For example, the expandable member 106 can include (e.g., contain) one or more reactants that are temporarily separated from one another within the interior volume. The interior volume is configured to facilitate a chemical reaction caused by mixing the reactants together (e.g., in response to actuation of the release means 108) to form a gas that causes expansion of the expandable member 106. The expandable member 106 can further include structure for contracting the expandable member 106 upon delivery of the fluid formulation 116 to facilitate excretion of the expandable member 106 from the subject. The expandable member 106 is configured to stretch a prescribed amount without perforating upon expansion.

[0061] The expandable member 106 can be formed from one or more materials. Examples of suitable materials for the expandable member 106 include hydroxypropyl methylcellulose (HPMC), polyvinyl acetate (PVA), lactide, glycolide, lactic acid, glycolic acid, per-dioxanone, trimethylene carbonate, caprolactone, and mixtures and copolymers thereof. The expandable member 106 can include one or more layers of material. The expandable member 106 can be a monolithic structure. In other embodiments, the expandable member 106 can be composed of one or more sections that are joined together (e.g., sealed or sutured).

[0062] The release means 108 is a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical-chemical structure. The release means 108 is a structure that causes expansion of the expandable member 106 upon actuation of the release means 108. 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 configured to degrade in water such that the release means 108 degrades upon contact with fluid 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. The release means 108 may be comprised of 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.

[0063] The delivery assembly 110 has a chemical, mechanical, electrical, electromechanical, electrochemical, chemical-mechanical, or electromechanical structure. In one or more embodiments, the delivery assembly 110 can include a housing 112, a membrane 114, a fluid formulation 116, a valve member 118, and a piston-needle assembly 120. In other embodiments, the delivery assembly 110 can include a housing 112, a membrane 114, a fluid formulation 116, a valve member 118, and a piston that does not include a needle. In these embodiments, the delivery assembly 110 is configured to deliver the fluid formulation 116 from the housing 112 as a fluid jet, the fluid jet having sufficient velocity to penetrate the GI lumen wall for systemic delivery of one or more therapeutic agents contained in the fluid formulation 116. Thus, when the discussion herein refers to the piston-needle assembly 120, it should be understood that the piston-needle assembly 120 can instead be a piston without a needle.

[0064] The delivery assembly 110 is a structure coupled to and disposed (partially or entirely) on the expandable member 106. In response to expansion of the expandable member 106, the delivery assembly 110 is further configured to deliver a fluid formulation 116 into the GI lumen wall or surrounding tissue via the piston-needle assembly 120 or as a fluid jet from the housing 112. The device 100 can include one or more delivery assemblies 110 coupled to the expandable member 106 to enable delivery of one or more fluid formulations.

[0065] The housing 112 is coupled to the expandable member 106 and configured to be in fluid communication with the expandable member 106. The housing 112 defines one or more chambers for movably receiving the piston-needle assembly 120. An outer portion of the housing 112 defines a recess that cooperates with the membrane 114 to define a reservoir for containing the fluid formulation 116. The housing 112 includes one or more fill ports for filling the reservoir with the fluid formulation 116. The housing 112 is configured to allow gas pressure from an interior of the expandable member 106 to be applied against a surface of the piston-needle assembly 120 to move the piston-needle assembly 120 axially relative to the housing 112. The housing 112 is further configured to interface with the valve member 118 (e.g., via one or more openings / seals) to allow the fluid formulation 116 to selectively flow from the reservoir into one or more chambers that are directed to the piston-needle assembly 120 for delivery into the GI lumen wall or into the surrounding tissue. The housing 112 may include one or more vent ports to act as pressure relief for the chambers of the housing 112. The housing 112 may include one or more components. In embodiments in which multiple components are included in the housing 112, the components may be co-located or physically separated from one another.

[0066] The membrane 114 is a flexible structure. The membrane 114 is coupled to the housing 112. The membrane 114 and the housing 112 cooperate to define a reservoir for containing the fluid formulation 116. The reservoir can define a volume for containing up to about 400 μL or more of fluid, including 400 μL of fluid. The reservoir may define a volume for containing about 50 μL to about 300 μL of fluid, including 50 μL to 300 μL of fluid, for example, 50 μL, 100 μL, 150 μL, 200 μL, 250 μL, or 300 μL of fluid, or any value therebetween, or may contain 300 μL, 350 μL, or 400 μL of fluid, or any value therebetween. The membrane 114 is further configured to expel the fluid formulation 116 from the reservoir into one or more chambers of the housing 112 in response to pressure applied against the outer surface of the membrane 114 (e.g., by gas generated inside the expandable member 106).

[0067] The membrane 114 may have any suitable shape, such as a torus, an ellipsoid, a sphere, a cube, or other shape. The membrane 114 may be formed from or may include a flexible or pliable material to allow deformation of the membrane 114 (e.g., bending / flexing under pressure) to expel the fluid formulation 116. Examples of suitable materials for the membrane 114 include polymeric materials (e.g., polyethylene terephthalate (PET)) or other flexible materials with sufficiently low moisture and gas permeability for use with the fluid formulation 116. The membrane 114 can be formed from a single material or a combination of materials. Additionally, the membrane 114 may include one or more layers of material. The membrane 114 may be a monolithic structure. In other embodiments, the membrane 114 may be comprised of multiple sections that are joined together (e.g., sealed or sewn) to define the membrane 114. The membrane 114 may include one or more components. In embodiments in which multiple components are included in membrane 114, the multiple components may be co-located or may be physically separated from one another.

[0068] A fluid formulation 116 is a formulation that includes one or more components, where the formulation is intended for a therapeutic, diagnostic, or other biological purpose. The fluid formulation 116 is in a fluid form, such as a liquid, a slurry, a gel, a suspension (including a colloidal suspension), a gas, a powder, or any combination thereof. The fluid formulation 116 may be a protein, peptide, polypeptide, antibody, drug (e.g., The composition may include one or more components comprising one or more therapeutic agents, such as one or more selected from immunosuppressants (e.g., adalimumab), chemotherapeutic agents, central nervous system (CNS) agents (e.g., anti-Parkinson's agents, anti-emetic agents), anti-diabetic agents (e.g., metformin), enzyme replacement therapy (ERT) agents), hormones (e.g., parathyroid hormone (PTH), follicle stimulating hormone (FSH), and analogs thereof), insulin, incretins or combinations thereof (e.g., GLP-1, GLP-2, GIP, glucagon, PYY, and analogs thereof), oligonucleotides (e.g., antisense oligonucleotides (ASO), RNA interference (RNAi), aptamer RNA), DNA or siRNA transcripts, cells, cytotoxic agents, vaccines or other prophylactic agents, nutritional supplements, vasodilators, or vasoconstrictors, delivery enhancers, retardants, excipients, diagnostic agents, or cosmetic enhancement agents. The fluid formulation 116 may contain a therapeutically effective amount of one or more therapeutic agents, as well as appropriate amounts of other ingredients (eg, excipients) to achieve a desired therapeutic effect in a subject.

[0069] The valve member 118 is a mechanical structure for selectively permitting the flow of the fluid formulation 116 from the reservoir into the housing 112. The valve member 118 is configured to be disposed within a chamber of the housing 112. The valve member 118 may be coupled to the housing 112. In other embodiments, the valve member 118 may be coupled to the piston-needle assembly 120 or may be integrally formed with the piston-needle assembly 120. The valve member 118 is further configured to permit the flow of the fluid formulation 116 from the reservoir into the chamber of the housing 112 in response to sufficient axial movement of the piston-needle assembly 120. For example, the housing 112 may include an opening extending between the reservoir and the piston chamber. A seal may be coupled to the opening to define a substantially fluid-tight seal between the reservoir and the piston chamber. The valve member 118 may be configured as a piercing member disposed within the piston chamber such that sufficient axial movement of the piston-needle assembly 120 relative to the housing 112 causes the piercing member to pierce the seal and allow the fluid formulation 116 to flow from the reservoir into the piston chamber.

[0070] According to another embodiment, the valve member 118 may be configured as a plug removably coupled to the housing 112 at an opening. In this embodiment, sufficient axial movement of the piston-needle assembly 120 relative to the housing 112 disengages the plug from the housing 112, providing a fluid passageway for the fluid formulation 116 to flow from the reservoir into the piston chamber.

[0071] Valve member 118 can be formed from a single material or a combination of materials. Examples of suitable materials for valve member 118 include polymeric materials (e.g., acrylonitrile butadiene styrene (ABS), polyetheretherketone (PEEK)), silicone, metals (e.g., stainless steel), or other materials or combinations of materials. Valve member 118 may include one or more components. In embodiments in which multiple components are included in valve member 118, the components may be co-located or physically separated from one another.

[0072] The piston-needle assembly 120 is a mechanical or chemomechanical structure. The piston-needle assembly 120 is movably (e.g., slidably) disposed within the housing 112. The piston-needle assembly 120 is configured to penetrate the GI luminal wall and deliver the fluid formulation 116 into the GI luminal wall or into the surrounding tissue. The piston-needle assembly 120 may have a length sufficient to penetrate to a desired depth into the GI luminal wall or surrounding tissue of the subject. For example, the piston-needle assembly 120 may have a length sufficient to penetrate through the GI luminal wall into the peritoneum or peritoneal cavity of the subject to expel the fluid formulation 116 therein.

[0073] The piston-needle assembly 120 may include one or more components. For example, the piston-needle assembly 120 may include a piston, a shaft, and a needle. The piston-needle assembly 120 may include an inlet for receiving the fluid formulation 116 from within the housing and a channel for directing the fluid formulation 116 to the GI lumen wall.

[0074] The needle may be at least partially degradable or may be entirely degradable so that the needle can degrade within the GI lumen upon delivery of the fluid formulation 116. Suitable materials for the needle include, for example, polyethylene oxide (PEO), magnesium, or other materials or combinations of materials. Suitable materials for the piston and shaft include, for example, polymeric materials (e.g., ABS), metals (e.g., titanium), or other materials or combinations of materials. In other embodiments, the needle may be substantially non-degradable or may include substantially non-degradable portions. In any embodiment, particularly in those in which the needle is substantially non-degradable, the delivery assembly 110 may include a return spring or other structure to allow retraction of the needle from the GI lumen wall within the housing 112 to prevent injury to the subject.

[0075] One or more components of the device 100 (e.g., the housing 102, the outer coating 104, the expandable member 106, the release means 108, the delivery assembly 110) may be formed from or include one or more biodegradable materials to facilitate the degradation of such components, e.g., to allow passage through the remainder of the subject's intestinal tract following delivery of the fluid formulation 116. Examples of biodegradable materials that may be suitable for use with various components of the 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.

[0076] The above description is an overview of ingestible device 100. The following description, with reference to Figures 2-12, relates to examples of various features and aspects of device 100. These examples are illustrative of device 100, but are not intended to be limiting.

[0077] 2, a cross-sectional view of device 200 (one embodiment of device 100) is illustrated in an unfolded and / or unrolled state. Device 200 is illustrated without housing 102 and optional outer coating 104. However, it should be understood that device 200 can be folded, rolled, and / or otherwise manipulated to be disposed within housing 102 (optionally with outer coating 104) to enable ingestion of device 200 and subsequent delivery to the GI tract.

[0078] Device 200 includes an expandable member in the form of a balloon 202 (an embodiment of expandable member 106), a deflation valve 212, a reactant reservoir 214 containing a first reactant 215, a release means 216 (an embodiment of release means 108), a second reactant 217, and a delivery assembly 300 (an embodiment of delivery assembly 110).

[0079] Referring again to FIG. 2, the balloon 202 includes an inflator portion 204, a deflator portion 205, a lower portion 206, and an elongated portion 210 extending between the inflator portion 204 and the deflator portion 205. The lower portion 206 extends downwardly (in the orientation shown in FIG. 2) between the inflator portion 204 and the deflator portion 205. The various portions of the balloon 202 cooperatively define an interior 202a for housing the various components of the device 200. As described below, the balloon 202 is structured to expand at a desired location within the lumen of the GI tract (e.g., stomach, intestines) in response to the production of gas from a chemical reaction between a first reactant 215 and a second reactant 217 within the interior 202a. In this manner, the balloon 202 can facilitate delivery of a fluid formulation 317 (an embodiment of the fluid formulation 116) from the delivery assembly 300 into the GI lumen wall or into the surrounding tissue.

[0080] The balloon 202 has a size and shape to occupy a space within the GI lumen upon inflation of the balloon 202 and enable delivery of the fluid formulation 317 into the GI lumen wall. For example, upon inflation of the balloon 202, the outer periphery of the balloon 202 (e.g., the outer periphery of the lower portion 206 and the elongated portion 210) presses against the surface of the lumen wall. The pressure exerted by the balloon 202 is sufficient to temporarily hold the balloon 202 against the lumen wall for delivery of the fluid formulation 317. Depending on the inner circumference of the lumen delivery site, the lower portion 206 may remain partially folded or may fully expand when the balloon 202 is inflated. For example, if the lumen is relatively large and there is no obstruction resisting the expansion of the balloon 202, the balloon 202 will assume a fully inflated configuration with the lower portion 206 fully expanded (as shown in FIG. 2). However, if the lumen is relatively small and the inner lumen circumference is smaller than the maximum size of the fully expanded balloon 202, the lower portion 206 will remain partially folded. In this manner, the balloon 202 can self-adjust to the size of the GI lumen to hold the balloon 202 in position for delivery of the fluid formulation 317, and the same balloon 202 can be used for a wide range of lumen sizes (e.g., different inner circumferences).

[0081] The deflation valve 212 is configured to cause deflation of the balloon 202 upon completion of delivery of the fluid formulation 317 into the GI lumen wall or surrounding tissue. In this manner, the deflation valve 212 can facilitate passage of the balloon 202 through the remainder of the GI tract and out the subject's anus. In the illustrated embodiment, the deflation valve 212 is configured as a degradable plug that temporarily covers an opening leading to the interior 202a. The degradable plug can be structured to degrade upon contact with fluids (e.g., bodily fluids) in the GI tract, thereby allowing gas contained in the interior 202a to exit through the opening. For example, the deflation valve 212 can be formed from or include an enteric material. The balloon 202 can include an optional flap 228 that can temporarily cover the deflation valve 212 to prevent premature activation (e.g., degradation) of the deflation valve 212 until the balloon 202 is inflated. For example, the flaps 228 can be temporarily held (e.g., glued, tacked, or otherwise held) in a folded position 228' about the flap fold axis 228a. Inflation of the balloon 202 can cause the flaps 228 to deploy from the folded position 228' to expose the deflation valve 212 and allow fluid within the GI tract to reach and cause the deflation valve 212 to disintegrate, thereby providing an opening for gas to escape to allow deflation.

[0082] Although the deflation valve 212 is shown disposed at the deflator portion 205, the deflation valve 212 may be disposed elsewhere on the expandable member 202 in other embodiments. Additionally, the balloon 202 may include multiple deflation valves 212. The deflation valve 212 may be configured differently than in the embodiment shown in FIG. 2. For example, in other embodiments, the deflation valve 212 may be configured as a dissolvable and / or movable cover disposed over an opening in the balloon 202. In these embodiments, dissolving and / or moving the cover away from the opening allows gas to exit the interior 202a through the opening, thereby enabling deflation.

[0083] The reactant reservoir 214 is disposed within the interior 202a and is structured to hold a first reactant 215 within the reactant reservoir 214 and temporarily prevent the first reactant 215 from contacting a second reactant 217 that is separately disposed within the interior 202a. The first reactant 215 may be, for example, citric acid. The second reactant 217 may be, for example, a carbonate such as potassium bicarbonate. In other embodiments, the first reactant 215 and the second reactant 217 may be other types of reactants (e.g., an acid and a base) that, when mixed, result in the formation of a gas sufficient to inflate the balloon 202. The second reactant 217 is shown disposed within the interior 202a of the inflator portion 204 near the first reactant 215. In other embodiments, the first reactant 215 and the second reactant 217 may be included in other regions of the balloon 202 so long as they are temporarily separated from one another.

[0084] The reactant reservoir 214 defines an interior volume for containing the first reactant 215. The reactant reservoir 214 can take a variety of different forms and shapes, such as a balloon or other structure. The reactant reservoir 214 is in selective fluid communication with the interior 202a via a reactant conduit 218 and a release means 216. The release means 216 is coupled to the reactant conduit 218 such that upon actuation (e.g., decomposition) of the release means 216, the first reactant 215 can exit the reactant reservoir 214 through the reactant conduit 218 to the interior 202a. For example, the release means 216 can be in the form of a degradable plug that blocks the interior of the reactant conduit 218 to temporarily prevent the first reactant 215 from entering the interior 202a. For example, when fluid in the GI tract contacts the release means 216 (upon decomposition of the housing 102 and / or outer coating 104), the release means 216 then decomposes allowing the reactant conduit 218 to discharge the first reactant 215 into the interior 202a.

[0085] In other embodiments, the device 200 includes a clip, band, or other structure for holding a portion of the balloon 202 to temporarily define separate chambers within the interior 202a for separately housing the first reactant 215 and the second reactant 217, respectively. For example, a portion of the balloon 202 can be clamped or compressed with a degradable clip or band to temporarily define multiple separate chambers within the interior 202a. The multiple chambers can be substantially sealed together to substantially prevent the first reactant 215 and the second reactant 217 from mixing. The clip or band can be positioned on an outer portion of the balloon 202 such that exposure to fluids within the GI tract (e.g., upon degradation of the housing 102 and / or the outer coating 104) causes the clip or band to degrade and then be released from the balloon 202. When the clip or band or similar structure is released from the balloon 202, the separate chambers are no longer substantially sealed together, allowing the first reactant 215 to mix with the second reactant 217 within the interior 202a.

[0086] Combining first reactant 215 with second reactant 217 within interior 202a causes a chemical reaction to occur forming a gas (e.g., CO2) that expands balloon 202 to an inflated state within the GI lumen and substantially aligns elongated portion 210 with a surface of the GI lumen wall. The substantial alignment of elongated portion 210 with the GI lumen wall advantageously helps to facilitate delivery of fluid formulation 317 from delivery assembly 300 into the GI lumen wall or surrounding tissue.

[0087] 2, delivery assembly 300 is coupled to balloon 202 and at least partially disposed within interior 202a. Delivery assembly 300 is shown to include housing 302 (an embodiment of housing 112), piercing member 308 (an embodiment of valve member 118), membrane 315 (an embodiment of membrane 114), fluid formulation 317 (an embodiment of fluid formulation 116), and piston-needle assembly 320 (an embodiment of piston-needle assembly 120). Membrane 315 and housing 302 cooperatively define reservoir 315a for containing fluid formulation 317.

[0088] As described below, the gas pressurizing the balloon 202 can pass through one or more openings in the housing 302 and exert pressure against a surface of the piston-needle assembly 320. When a threshold pressure is reached (e.g., upon full or partial inflation of the balloon 202), the pressure causes the piston-needle assembly 320 to move relative to the housing 302 and advance a portion of the piston-needle assembly 320 into the GI lumen wall or into the surrounding tissue. The gas pressurizing the balloon 202 is also applied against the exterior surface of the membrane 315 to expel the fluid formulation 317 into the housing 302. However, the reservoir 315a is substantially fluid-tight from the housing 112 to prevent flow of the fluid formulation 317 from the reservoir 315a to the piston-needle assembly 320 until the piston-needle assembly 320 has moved a sufficient distance. Upon sufficient axial movement of the piston-needle assembly 320 relative to the housing 302 (e.g., upon penetrating the GI lumen wall), the penetrating member 308 is configured to puncture a seal on the housing 302 to allow the fluid formulation 317 to flow from the reservoir 315a into the housing 302 and through the piston-needle assembly 320 for delivery to the GI lumen wall or surrounding tissue.

[0089] 3, a detailed view of a portion of device 200 is shown, including a delivery assembly 300. As shown in FIG. 3, delivery assembly 300 includes housing 302, optional chamber seal 306, reservoir seal 307, piercing member 308, needle seal 309, cover 310, membrane 315, fluid formulation 317, and piston-needle assembly 320. Piston-needle assembly 320 is collectively defined by piston 322, needle 324, and shaft 326. In other embodiments, piston-needle assembly 320 is a monolithic structure including piston 322, needle 324, and shaft 326.

[0090] 3-5, the housing 302 includes a peripheral wall 302a that defines a piston chamber 302a′ and a needle chamber 302a″. The piston 322 is movably (e.g., slidably) disposed within the piston chamber 302a′. The needle 324 and a portion of the shaft 326 are disposed within the needle chamber 302a″. In the orientation shown in FIG. 3, the needle chamber 302a″ extends from an upper end of the piston chamber 302a′. The piston chamber 302a′ has a substantially cylindrical shape that defines a first inner diameter D1 that corresponds to an outer diameter of the piston 322. Similarly, the needle chamber 302a″ has a substantially cylindrical shape that defines a second inner diameter D2 that corresponds to an outer diameter of the needle 324 and the shaft 326. However, it should be understood that the piston chamber 302a′ and the needle chamber 302a″ may have different shapes other than cylindrical (e.g., ovoid, spherical) according to other embodiments. 3, the first inner diameter D1 is larger than the second inner diameter D2 such that the peripheral wall 302a defines a step region 302aa extending between an upper end of the piston chamber 302a' and a lower end of the needle chamber 302a''. The piston chamber 302a' and the needle chamber 302a'' cooperate to define a longitudinal axis 302ab along which the piston-needle assembly 320 moves axially.

[0091] The housing 302 further includes an upper wall 302b extending outwardly (e.g., radially) from an upper portion of the peripheral wall 302a that defines the needle chamber 302a". The housing 302 is structured to be coupled (e.g., heat sealed, glued) to the balloon 202 (e.g., elongated portion 210) at the upper wall 302b. In an assembled state, a portion of the peripheral wall 302a above the upper wall 302b extends outwardly from the elongated portion 210 of the balloon 202 to position the needle chamber 302a" adjacent to the GI lumen wall. The upper wall 302b and the portion of the peripheral wall 302a (extending from the upper wall 302b to the step region 302aa) collectively define a recess 304 that extends circumferentially around the needle chamber 302a". As described below, the membrane 315 is coupled to the housing 302 such that the membrane 315 surrounds the recess 304 and defines a reservoir 315a for containing a fluid formulation 317 therein.

[0092] The top wall 302b further defines one or more fill ports 302b' for filling the reservoir 315a with the fluid formulation 317. For example, in the illustrated embodiment, the top wall 302b defines two fill ports 302b' configured as through holes for filling (e.g., partially or completely) the reservoir 315a with the fluid formulation 317. After filling the reservoir 315a, the fill ports 302b' are substantially fluid-tight with a separate seal 303 bonded thereto. The seal 303 may include, for example, silicone or aluminum foil. For example, the seal 303 may include a tube inserted into each fill port 302b' and a plug engaged to the side of the tube through a side opening of the housing 302 to form a pinch valve structure. In other embodiments, the fill port 302b' may include a septum (e.g., a silicone septum) such that the fill port 302b' may self-seal after filling the reservoir 315a with the fluid formulation 317. In any event, the reservoir 315a may be filled with the fluid formulation 317 before the delivery assembly 300 is coupled to the balloon 202. This advantageously provides flexibility for aseptic assembly of the device 200. For example, the reservoir 315a may be substantially evacuated by drawing a vacuum through the fill port 302b' in a sterile environment prior to coupling the delivery assembly 310 to the balloon 202. The evacuated reservoir 315a may then be filled with the fluid formulation 317 through the fill port 302b' in a sterile environment prior to assembly with the balloon 202.

[0093] 3-5, the peripheral wall 302a further defines an opening 302a''' at the step region 302aa that extends between the reservoir 315a and the piston chamber 302a'. The reservoir seal 307 is coupled (e.g., glued) to the peripheral wall 302a at the opening 302a''' to define a substantially fluid-tight seal between the reservoir 315a and the piston chamber 302a'. In this manner, the reservoir seal 307 substantially prevents the fluid formulation 317 from entering the piston chamber 302a' from the opening 302a'''. The reservoir seal 307 can be formed from a penetrable material, such as aluminum foil.

[0094] The peripheral wall 302a and / or the top wall 302b may further define one or more vent ports for venting the piston chamber 302a' or the balloon interior 202a during or after axial movement of the piston-needle assembly 320. The vent ports may be in selective fluid communication with the GI lumen environment exterior to the device 200. Additionally or alternatively, the peripheral wall 302a may include a ramp or other localized protrusion extending from its inner surface to press against the piston seal 323 upon sufficient axial movement of the piston 322 to form a fluid path through the piston chamber 302a' and allow venting of the balloon interior 202a to the GI lumen environment.

[0095] The penetrating member 308 is disposed within the piston chamber 302a'. In the embodiment shown in Figures 3-5, the penetrating member 308 is coupled to the peripheral wall 302a adjacent the reservoir seal 307 by an adhesive tape 305 (e.g., polyimide tape). In other embodiments, the penetrating member 308 may be coupled to the peripheral wall 302a by, for example, heat staking, ultrasonic welding, or other attachment means. In the embodiment shown in Figures 3-5, the penetrating member 308 is configured as an elongated shaft having a tapered end (e.g., a pointed tip) similar to the structure of a stud. The penetrating member 308 may be made, for example, from a polymeric material (e.g., polyetheretherketone (PEEK)), a metal (e.g., stainless steel), or other material or combination of materials. In the embodiment shown in Figures 3-5, the tapered end of the penetrating member 308 is positioned adjacent the reservoir seal 307 by an adhesive tape 305 attached to the inner surface of the peripheral wall 302a. As described below with reference to FIG. 6, the tapered end is configured to pierce the reservoir seal 307 in response to sufficient axial movement of the piston-needle assembly 320 relative to the housing 302, allowing the fluid formulation 317 to flow from the reservoir 315a into the piston chamber 302a'.

[0096] Another embodiment of the valve member 118 is shown in FIGS. 7-8 as a piercing member 408. In this embodiment, the piercing member 408 is configured as a flexible tab. The piercing member 408 may be made, for example, from a metal (e.g., stainless steel), a polymeric material (e.g., PEEK), or other material or combination of materials. The piercing member 408 includes a planar end 408a that defines an opening 408a′ for coupling the piercing member 408 to the peripheral wall 302a in the piston chamber 302a′. For example, the piercing member 408 may be heat staked, ultrasonically welded, glued, or otherwise attached to the peripheral wall 302a at the planar end 408a. The piercing member 408 further includes an elongated portion 408b that extends away from the planar end 408a. The elongated portion 408b has a generally arcuate shape and extends downward (in the orientation shown in FIG. 8) at an acute angle relative to the planar end 408a. The arcuate shape of the elongated portion 408b may help avoid interference between the piercing member 408 and the opening 302a''' when penetrating the reservoir seal 307, thereby allowing for substantially unimpeded flow of the fluid formulation 317 into the piston chamber 302a'. The elongated portion 408b may also include one or more openings (e.g., slots) to further allow the fluid formulation 317 to flow through the openings 302a'''.

[0097] The piercing member 408 further includes a tapered portion 408c extending from the elongated portion 408b. The tapered portion 408c extends upwardly at an acute angle (as oriented in FIG. 8) toward the planar end 408a. The tapered portion 408c terminates in a pointed end. The piercing member 408 is configured to allow the tapered portion 408c to pierce the reservoir seal 307 upon sufficient axial movement of the piston-needle assembly 320 within the piston chamber 302a'. For example, as shown in FIG. 8, when the piston 322 moves axially within the piston chamber 302a', a portion of the piston 322 may engage the elongated portion 408b, causing the elongated portion 408b to deform or bend (either elastically or permanently) relative to the planar end 408a. As a result, the tapered portion 408c can move toward and penetrate the reservoir seal 307, thereby allowing the fluid formulation 317 to flow through the opening 302a'' and into the piston chamber 302a'.

[0098] According to another embodiment, the valve member 118 may be configured as a cartridge including a needle (or other feature having a pointed end) sufficient to penetrate the reservoir seal 307. The cartridge may be coupled to the peripheral wall 302a at least partially within the opening 302a''' adjacent the reservoir seal 307. The cartridge may be configured such that when the piston-needle assembly 320 engages the cartridge during axial movement of the piston-needle assembly 320, the needle (or other feature) of the cartridge can move toward and puncture the reservoir seal 307.

[0099] According to another embodiment, the valve member 118 may be defined by a portion of the piston-and-needle assembly 320. For example, the top of the piston 322 may include an outwardly extending protrusion or other structural feature for piercing the reservoir seal 307 when the piston-and-needle assembly 320 moves a sufficient axial distance within the piston chamber 302a'. The protrusion or other feature may be coupled to the piston 322 or the shaft 326 or may be integrally formed with the piston 322 or the shaft 326.

[0100] According to another embodiment shown in FIGS. 9-10, the valve member 118 is in the form of a plug 508 instead of a piercing member. The plug 508 is removably coupled to the housing 302 at the opening 302a'''. The plug 508 is shown to include a body 508a and a seal 508b coupled to or integrally formed with the body 508a. In other examples, the plug 508 may be of unitary construction. In the illustrated example, the seal 508b is configured to engage the housing 302 at the opening 302a''' and form a substantially fluid-tight seal therebetween. For example, the seal 508b may be formed from or include a flexible polymeric material such as silicone. The body 508a has a tapered (e.g., conical) elongated structure to create an interference fit with the housing 302 at the opening 302a''', thereby helping to retain the plug 508 on the housing 302. A portion of the body 508a extends into the piston chamber 302a' for engaging a surface of the piston 322 during axial movement of the piston 322. In this manner, the piston 322 can force the plug 508 out of the housing 302 and provide a fluid passageway from the reservoir 315a through the opening 302a''' to the piston chamber 302a' for expelling the fluid formulation 317.

[0101] For example, as shown in Figure 10, the piston-needle assembly 320 is moved a sufficient distance relative to the piston chamber 302a' such that the upper surface of the piston 322 engages the body 508a of the plug 508. As a result, the plug 508 is pushed out of the opening 302a''' away from the housing 302, as indicated by the unidirectional arrow 510 in Figure 10, thereby providing a fluid passageway for the flow of the fluid formulation 317 from the reservoir 315a through the opening 302a''' to the piston chamber 302a'.

[0102] 3-5, the membrane 315 is coupled to the housing 302 to define a reservoir 315a. For example, the membrane 315 may be coupled to the housing 302 by heat sealing, ultrasonic welding, gluing, or other means. In the illustrated embodiment, the membrane 315 is coupled to an outer portion of the top wall 302b and an outer portion of the peripheral wall 302a. The membrane 315 extends circumferentially of the needle chamber 302a'' and surrounds the recess 304. In this manner, the membrane 315, the peripheral wall 302a, and the top wall 302b cooperatively define a reservoir 315a for containing the fluid formulation 317 therein. The reservoir 315a can contain up to about 400 μL or more of fluid, including 400 μL of fluid. Reservoir 315a may contain between about 50 μL and about 300 μL of fluid, such as between about 50 μL, 100 μL, 150 μL, 200 μL, 250 μL, or 300 μL of fluid, or any value therebetween, or may contain between about 300 μL, 350 μL, or 400 μL of fluid, or any value therebetween. As described below, membrane 315 is configured to deform (e.g., compress) due to gas pressure generated within balloon 202 (due to reaction between first reactant 215 and second reactant 217) to expel fluid formulation 317 from reservoir 315a. The membrane 315 may have a relaxed or surface shape that is complementary to the exterior shape of the housing 302 defining the recess 304 (i.e., when the reservoir 315a is not filled with the fluid formulation 317) such that the membrane 315 can deform sufficiently to expel a substantial portion of the fluid formulation 317 from the reservoir 315a. Furthermore, such complementary shapes of the membrane 315 may help facilitate sufficient drainage of the reservoir 315a for subsequent filling with the fluid formulation 317 during assembly. The membrane 315 may be formed from a polymeric material (e.g., polyethylene terephthalate (PET)) or other flexible material or combination of materials that have sufficiently low moisture and gas permeability for use with the fluid formulation 317.

[0103] Optionally, a membrane shield may be coupled to the housing 302 to protect the membrane 315 from potential damage, for example, during the assembly process of the device 200. The membrane shield may substantially surround an outer surface of the membrane 315. The membrane shield may be formed from a rigid or semi-rigid polymeric material and may define a number of openings that provide a fluid path for gas within the interior 202a to be applied to the outer surface of the membrane 315.

[0104] Piston-needle assembly 320 is disposed within housing 302 and configured to move axially relative to housing 302 along longitudinal axis 302ab. Piston-needle assembly 320 is collectively defined by at least a piston 322, a needle 324, and a shaft 326. Piston-needle assembly 320 may further include a piston seal 323 and a shaft seal 325. In other embodiments, piston-needle assembly 320 is a monolithic structure including piston 322, needle 324, and shaft 326.

[0105] The piston 322 is movably (e.g., slidably) disposed within the piston chamber 302a'. The piston 322 defines an upper surface 322a and a lower surface 322b. The piston 322 is temporarily held in an axial position within the piston chamber 302a' by a release mechanism defined by the cover 310. The piston 322 is configured to move axially within the piston chamber 302a' in response to a threshold gas pressure applied against the lower surface 322b within the balloon 202. The piston seal 323 is coupled to or integrally formed (e.g., insert molded) with a peripheral side of the piston 322 between the upper surface 322a and the lower surface 322b. The piston seal 323 is configured to engage an inner surface of the peripheral wall 302a, thereby forming a substantially fluid-tight seal between the piston 322 and the peripheral wall 302a within the piston chamber 302a'. In this manner, the piston seal 323 can help to substantially prevent fluid (e.g., air, fluid formulation 317) from entering or exiting the region of the piston chamber 302a' located above the upper surface 322a. The piston seal 323 is further configured to allow axial movement of the piston 322 along the longitudinal axis 302ab relative to the peripheral wall 302a within the piston chamber 302a'. The piston 322 may be formed from a polymeric material (e.g., acrylonitrile butadiene styrene (ABS)), or other material or combination of materials. The piston seal 323 can be formed from silicone or other suitable material.

[0106] The needle 324 is coupled (e.g., press-fit) to the shaft 326 and the piston 322 or integrally molded (e.g., insert-molded) therewith. In the unactuated state shown in FIG. 3, the needle 324 is temporarily positioned within the needle chamber 302a″. The needle seal 309 is coupled (e.g., glued) to the peripheral wall 302a″ at the upper end of the needle chamber 302a″ to substantially prevent fluids within the GI tract from entering the needle chamber 302a″ until the needle 324 pierces the needle seal 309. The needle seal 309 can be formed from a penetrable material (e.g., aluminum foil) to allow the needle 324 to penetrate the needle seal 309. In this manner, the needle seal 309 and the peripheral wall 302a can cooperatively define a substantially sterile environment within the needle chamber 302a″ for containing the needle 324 prior to delivery of the fluid formulation 317 into the GI lumen wall or into the surrounding tissue.

[0107] As shown in FIGS. 3-5, the needle 324 includes a tapered portion 324a (e.g., a pointed tip) configured to pierce the needle seal 309 and penetrate the GI lumen wall in response to sufficient axial movement of the piston 322. The needle 324 further includes an elongated portion 324b extending from the tapered portion 324a. The elongated portion 324b may be coupled to the tapered portion 324a or may be integrally formed with the tapered portion 324a. The elongated portion 324b defines a needle channel 324b' extending from the needle opening 324a' to an opposite end of the elongated portion 324b. As shown in FIG. 3, the tapered portion 324a defines a needle opening 324a' extending through the end of the tapered portion 324a for ejecting the fluid formulation 317 into the GI lumen wall or into the surrounding tissue. Additionally or alternatively, the elongated portion 324b includes a side opening (e.g., a slotted opening) for ejecting the fluid formulation 317 into the GI lumen wall or into the surrounding tissue. In some embodiments, the needle 324 may be at least partially degradable or fully degradable such that at least a portion of the needle 324 can substantially degrade within the GI lumen wall (or elsewhere in the GI tract) upon delivery of the fluid formulation 317. For example, the needle 324 may be formed from or otherwise include polyethylene oxide (PEO), magnesium, or other degradable material or combination of materials.

[0108] In other embodiments, the needle 324 can be formed from or otherwise include a substantially non-degradable material or combination of materials, such as polyetheretherketone (PEEK). In these and other embodiments, the needle 324 can include a tip formed from a degradable material, such as magnesium, to allow for biodegradation of at least the tip within the patient's body. In embodiments in which the needle 324 is substantially non-degradable or includes a substantially non-degradable portion, the device 200 is structured to retract the needle 324 within the housing 302 upon completing delivery of the fluid formulation 317. For example, the device 200 can include a return spring or other biasing member coupled to the needle 324 to retract the needle 324 into the housing 302 after delivery of the fluid formulation 317.

[0109] The shaft 326 is coupled (e.g., press-fit, glued) to or integrally formed with the piston 322 and the needle 324. In one or more embodiments, the shaft 326 and the piston 322 may define a monolithic structure. In the illustrated embodiment, the shaft 326 is configured as a substantially cylindrical member having a generally elongated configuration, although other shapes and configurations are contemplated in other embodiments. The shaft 326 extends from a first end 326a to a second end 326b. The first end 326a is coupled (e.g., press-fit, glued, insert molded) to or integrally formed with the needle 324. The second end 326b is coupled to or integrally formed with the piston 322. The shaft 326 further defines an inlet 326b' for receiving the fluid formulation 317 from the piston chamber 302a' and an inner shaft channel 326a' for directing the fluid formulation 317 from the inlet 326b' to the needle channel 324b'. The inlet 326b' extends radially from an outer surface of the shaft 326 to the inner shaft channel 326a'. The inner shaft channel 326a' extends longitudinally along the longitudinal axis 302ab. In other embodiments, the shaft 326 may include multiple inlets and / or channels for directing the fluid formulation 317 to the needle channel 324b'.

[0110] The shaft seal 325 is coupled (e.g., press-fit, glued) or integrally molded (e.g., insert molded) with an outer portion of the shaft 326. The shaft seal 325 is disposed on a circumferential ridge 326e of the shaft 326 above the inlet 326c. The shaft seal 325 is configured to engage an inner surface of the peripheral wall 302a between the piston chamber 302a' and the needle chamber 302a'' to form a substantially fluid-tight seal between the piston chamber 302a' and the needle chamber 302a'' upon sufficient axial movement of the piston-needle assembly 320 relative to the housing 302. In this manner, the shaft seal 325 may aid in preventing the fluid formulation 317 from entering the needle chamber 302a'' from the piston chamber 302a'. The shaft seal 325 can also function to limit axial movement of the piston-needle assembly 320 within the piston chamber 302a' to help define a fluid channel 312 (see FIG. 6) between an upper surface of the piston 322 within the piston chamber 302a' and an inner surface of the peripheral wall 302a. As described below with reference to FIG. 6, the fluid channel 312 can function to direct the fluid formulation 317 from the opening 302a''' to an inlet 326c within the piston chamber 302a'. In other embodiments, the piston 322 can define a fluid channel in the upper surface 322a for directing the fluid formulation 317 to the inlet 326c.

[0111] In other embodiments, the housing 302 and / or the piston 322 may include one or more features (e.g., standoff features, stop features, protrusions) to limit axial movement of the piston-needle assembly 320 within the piston chamber 302a' to help define the fluid channel 312.

[0112] The delivery assembly 300 optionally includes a lubricant seal 306 coupled to an inner surface of the peripheral wall 302a within the piston chamber 302a'. The lubricant seal 306 can help minimize interaction between the fluid formulation 317 and any lubricant that may be present within the piston chamber 302a' (e.g., on the piston seal 323), which can help minimize contamination of the fluid formulation 317. As shown in FIG. 5, the lubricant seal 306 extends circumferentially within the piston chamber 302a'. In other embodiments, the lubricant seal 306 is coupled to the piston-needle assembly 320.

[0113] The cover 310 is coupled to the housing 302 at the open end of the piston chamber 302a'. The cover 310 is also releasably coupled to the piston-needle assembly 320 by a release mechanism that temporarily holds the piston-needle assembly 320 in an axial position within the piston chamber 302a'. For example, in the embodiment shown in FIGS. 3-5, the cover 310 includes a first cover portion 310a coupled to the peripheral wall 302a and a second cover portion 302b coupled (e.g., heat staking, ultrasonic welding) to the piston-needle assembly 320. The first cover portion 310a is releasably coupled to the second cover portion 310b by one or more tabs 310c that define the release mechanism. For example, the tabs 310c can define a flange connection between the first cover portion 310a and the second cover portion 310b.

[0114] As shown in FIG. 5, the tabs 310c are circumferentially spaced about the second cover portion 310b to define a plurality of openings 310a′. The openings 310a′ may allow gas generated within the interior 202a of the balloon 202 to be applied to the underside 322b of the piston 322. According to other embodiments, the cover 310 may include one or more openings disposed in other portions of the cover 310. When a threshold gas pressure is applied to the piston 322, the tabs 310c are configured to disengage from at least one of the first cover portion 310a or the second cover portion 310b, thereby allowing the piston-needle assembly 320 to move axially along the longitudinal axis 302ab within the piston chamber 302a′ toward the piercing member 308. The threshold pressure value may be a pressure associated with a fully inflated state of the balloon 202 such that the elongated portion 210 is substantially aligned against the GI lumen wall before the needle 324 advances into the GI lumen wall, e.g., before the tab 310c disengages to allow the piston-needle assembly 320 to move axially toward the penetrating member 308.

[0115] According to another embodiment, the release mechanism of cover 310 may be defined by one or more snap features that releasably couple cover 310 to piston-needle assembly 320. The one or more snap features may be structured to disengage from piston-needle assembly 320 and / or cover 310 in response to a threshold gas pressure applied against piston-needle assembly 320 such that piston-needle assembly 320 can move axially away from cover 310 and toward piercing member 308 to advance needle 324 into the GI lumen wall, similar to tab 310c described above.

[0116] According to another embodiment, the release mechanism of the cover 310 may be defined by one or more flexible tabs extending from the cover 310 toward the longitudinal axis 302ab. The one or more flexible tabs may overlap a complementary feature (e.g., a protrusion) on the piston-needle assembly 320 to define an interference condition. In this embodiment, the one or more tabs deflect in response to a threshold gas pressure applied against the piston-needle assembly 320, causing the piston-needle assembly 320 to overcome the interference condition with the one or more tabs and allow the piston-needle assembly 320 to move axially away from the cover 310 and toward the piercing member 308 to advance the needle 324 into the GI lumen wall.

[0117] 6, a portion of device 200 including delivery assembly 300 is illustrated after device 200 has reached a desired location in the GI tract (e.g., stomach or small intestine) for delivering fluid formulation 317. As shown in FIG. 6, balloon 202 has been inflated by gas generated within interior 202a such that elongated portion 210 is substantially aligned with the GI lumen wall. Gas generated within interior 202a applies pressure (indicated by unidirectional arrow 330) through the exterior surface of membrane 315 and opening 310a′ in cover 310 against underside 322b of piston 322. When the gas pressure reaches a threshold value (e.g., a pressure associated with a fully or partially inflated state of the balloon 202), the piston 322 disengages from the cover 310 via the removable tab 310c, thereby allowing the piston-needle assembly 320 to move axially along the longitudinal axis 302ab relative to the housing 302 and toward the piercing member 308 such that the needle 324 punctures the needle seal 309 and penetrates the GI lumen wall. In this embodiment, the fluid formulation 317 remains within the reservoir 315a while gas pressure is applied against the exterior surface of the membrane 315 until the needle 324 has sufficiently penetrated the GI lumen wall or surrounding tissue (e.g., to a desired penetration depth).

[0118] Once the needle 324 has sufficiently penetrated the GI lumen wall or surrounding tissue, the piston 322 engages the piercing member 308, which punctures the reservoir seal 307. As a result, gas pressure within the interior 202a applied against the outer surface of the membrane 315 causes the fluid formulation 317 to flow from the reservoir 315a through the opening 302a'''' and into the piston chamber 302a'. The fluid formulation 317 is directed through the fluid channel 312 to the inlet 326b' of the shaft 326. The piston seal 323 and the shaft seal 325 help contain the fluid formulation 317 within the fluid channel 312. The gas pressure applied against the membrane 315 further causes the fluid formulation 317 to flow through the inlet 326b', the inner shaft channel 326a', and the needle channel 324b' such that the needle 324 expels the fluid formulation 317 through the needle opening 324a' into the GI lumen wall or surrounding tissue. In this manner, one or more therapeutic agents contained in the fluid formulation 317 may be delivered into the subject's bloodstream.

[0119] In other embodiments, the device 200 may be configured such that the fluid formulation 317 is expelled into the piston chamber 302a' substantially simultaneously as the needle 324 penetrates the GI luminal wall. For example, this may be accomplished by selecting the length of the needle 324, the length of the shaft 326, the position of the piercing member 308, the dimensions of the housing 302, or otherwise adjusting the amount of axial movement of the piston-needle assembly 320 within the piston chamber 302a' such that the amount of movement required to puncture the seal 307 via the piercing member 308 substantially matches the amount of movement required for the needle 324 to penetrate the GI luminal wall. Configuring the device 200 such that the piercing member 308 penetrates the seal 307 after or substantially simultaneously as the needle 324 penetrates the GI luminal wall may advantageously help prevent expulsion of the fluid formulation 317 into the luminal environment to ensure delivery of a significant portion of the fluid formulation 317 into the GI luminal wall or into the surrounding tissue. In other words, the device 200 allows for the penetration of the GI luminal wall and the ejection of the fluid formulation 317 to occur in a sequential manner, substantially avoiding the ejection of the fluid formulation 317 into the luminal environment.

[0120] Once delivery of the fluid formulation 317 is complete, the needle 324, along with one or more additional components of the device 200 (e.g., the housing 302, the membrane 315, the shaft 326, the piston 322, the cover 310), may then disintegrate within the GI lumen wall or other area within the GI lumen. For example, the device 200 may include a return spring or other biasing member coupled to the needle 324 to pull the needle 324 back into the housing 302 after delivery of the fluid formulation 317. In any of these embodiments, the deflation valve 212 may release a substantial amount of the gas contained within the interior 202a to permit substantial deflation of the balloon 202 and subsequent traversal of the device 200 through the remainder of the GI tract and out the subject's anus.

[0121] 11, a method 600 of delivering a fluid formulation 116 to a subject's GI tract using the device 100 is shown. In a first step, the subject ingests the device 100 (e.g., by swallowing the device 100) (step 601). As a result of ingestion, the housing 102 and / or the outer coating 104 are at least partially (or completely) degraded as the device 100 reaches a desired location in the GI tract for delivery of the fluid formulation 116 (step 602). In response to the degradation of the housing 102 and / or the outer coating 104, the release means 108 is actuated to expand the expandable member 106 within the GI lumen (step 603). Expansion of the expandable member 106 within the GI lumen positions the delivery assembly 110 adjacent to the GI lumen wall (step 604). When the gas pressure within the expandable member 106 reaches a threshold value, the gas pressure causes the piston-needle assembly 120 to move relative to the housing 112 such that a portion of the piston-needle assembly 120 penetrates into the GI lumen wall or into the surrounding tissue (step 605). When the piston-needle assembly 120 has moved a sufficient axial distance relative to the housing 112, the valve member 118 opens to allow the fluid formulation 116 to enter the housing 112 (step 606). In this manner, the device 100 can deliver one or more therapeutic agents contained in the fluid formulation 116 to the bloodstream of the subject for systemic delivery.

[0122] 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, the 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.

[0123] 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. Furthermore, 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 positively described, the embodiment of the present invention specifically contemplates excluding that component, value, property, component, feature, step, etc. The illustrations are not necessarily drawn to scale. There may be a distinction between the artistic depictions in the present disclosure and the actual device due to variables in the manufacturing process, etc. There may 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, further divided, or reordered 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. 1. A delivery assembly for an ingestible device for delivering a fluid formulation into a gastrointestinal (GI tract) cavity wall or surrounding tissue of a subject, comprising: a housing defining a chamber; a piston and needle assembly movably disposed within the chamber, the piston and needle assembly including an inlet and a flow passage; a membrane coupled to the housing to cooperate with the housing to define a reservoir for containing a fluid formulation, the housing further defining an opening extending between the chamber and the reservoir; a valve member for selectively controlling flow of the fluid formulation from the reservoir through the opening to the chamber; in response to sufficient movement of the piston-needle assembly relative to the housing, the valve member opens to allow the fluid formulation to flow from the reservoir, through the opening and into the chamber; A delivery assembly, wherein the fluid formulation is directed from the chamber to the inlet and to the channel for delivery into the GI lumen wall or into the surrounding tissue.

2. The delivery assembly of claim 1 , wherein the piston-needle assembly and the housing cooperatively define a fluid channel within the chamber for directing the fluid formulation from the opening to the inlet.

3. The delivery assembly of claim 1 , wherein the valve member comprises a plug removably coupled to the housing at the opening.

4. 4. The delivery assembly of claim 3, wherein the piston-needle assembly engages and disengages the plug from the housing to allow the fluid formulation to flow from the reservoir through the opening and into the chamber.

5. The delivery assembly of claim 1 , wherein the valve member comprises a piercing member and a seal, the seal being coupled to the housing at the opening.

6. 6. The delivery assembly of claim 5, wherein the piston-needle assembly engages the piercing member to cause the piercing member to pierce a seal and allow the fluid formulation to flow from the reservoir through the opening and into the chamber.

7. The delivery assembly of claim 5 , wherein the penetrating member is configured as a flexible tab having a tapered end.

8. The delivery assembly of claim 5 , wherein the penetrating member is configured as an elongate shaft having a tapered end.

9. The delivery assembly of claim 1 , wherein the delivery assembly is configured to be coupled to an expandable member and disposed within the expandable member.

10. The delivery assembly of claim 1 , wherein the delivery assembly is configured to be contained in an ingestible housing for delivery to the GI tract of the subject.

11. 2. The delivery assembly of claim 1, wherein the piston-needle assembly is configured to move relative to the housing in response to gas pressure applied against a surface of the piston-needle assembly to advance a portion of the piston-needle assembly into the GI lumen wall or into surrounding tissue.

12. 2. The delivery assembly of claim 1, wherein the piston-needle assembly is configured to penetrate through the GI lumen wall into the peritoneum or peritoneal cavity of the subject to expel the fluid formulation into the peritoneum or peritoneal cavity of the subject.

13. The delivery assembly of claim 1 , wherein the reservoir defines a volume containing up to about 400 μL of fluid.

14. The delivery assembly of claim 1 , wherein the reservoir defines a volume containing from about 50 μL to about 300 μL of fluid.

15. The delivery assembly of claim 1 , further comprising a cover coupled to the housing, the cover defining a release mechanism for temporarily holding the piston-needle assembly in an axial position relative to the housing.

16. 16. The delivery assembly of claim 15, wherein the cover includes a first cover portion coupled to the housing and a second cover portion coupled to the piston-needle assembly, and the release mechanism is defined by one or more tabs releasably coupled between the first cover portion and the second cover portion.

17. 17. The delivery assembly of claim 16, wherein the cover further comprises one or more openings to allow gas pressure to be applied against a surface of the piston-needle assembly, and the one or more tabs are configured to disengage from at least one of the first cover portion or the second cover portion to allow the piston-needle assembly to move axially relative to the housing in response to the gas pressure reaching a threshold value.

18. The delivery assembly of claim 1 , wherein the membrane extends circumferentially about the housing.

19. The delivery assembly of claim 1 , wherein the membrane is made of a flexible material that allows deformation of the membrane by gas pressure applied against an outer surface of the membrane to expel the fluid formulation from the reservoir into the chamber.

20. The delivery assembly of claim 1 , wherein the housing includes one or more fill ports for filling the reservoir with the fluid formulation.

21. The delivery assembly of claim 1 , further comprising the fluid formulation disposed in the reservoir, the fluid formulation comprising at least one therapeutic agent.

22. 22. The delivery assembly of claim 21, wherein the at least one therapeutic agent is one or more selected from an immunosuppressant, a chemotherapeutic agent, a central nervous system (CNS) drug, an antidiabetic drug, an enzyme replacement therapy (ERT) drug, an antibody, a hormone, insulin, an incretin or a combination thereof, or an oligonucleotide.

23. 1. An ingestible device for delivering a fluid formulation into a GI tract lumen wall or surrounding tissue of a subject, the ingestible device comprising: An expandable member; a delivery assembly coupled to and disposed within the expandable member, The delivery assembly comprises: a housing defining a chamber; a piston and needle assembly movably disposed within the chamber, the piston and needle assembly including an inlet and a flow passage; a membrane coupled to the housing to cooperate with the housing to define a reservoir for containing a fluid formulation, the housing further defining an opening extending between the chamber and the reservoir; a valve member for selectively controlling flow of the fluid formulation from the reservoir through the opening and into the chamber; the fluid formulation disposed within the reservoir, the fluid formulation including at least one therapeutic agent; in response to sufficient movement of the piston-needle assembly relative to the housing, the valve member opens to allow the fluid formulation to flow from the reservoir, through the opening and into the chamber; An ingestible device, wherein the fluid formulation is directed from the chamber to the inlet and to the channel for delivery into the GI lumen wall or into the surrounding tissue.

24. 24. The device of claim 23, wherein the piston-needle assembly and the housing cooperatively define a fluid channel within the chamber for directing the fluid formulation from the opening to the inlet.

25. The device of claim 23 , wherein the valve member comprises a plug removably coupled to the housing at the opening.

26. 26. The device of claim 25, wherein the piston and needle assembly engages and disengages the plug from the housing to allow the fluid formulation to flow from the reservoir through the opening and into the chamber.

27. 24. The device of claim 23, wherein the valve member comprises a piercing member and a seal, the seal being coupled to the housing at the opening.

28. 28. The device of claim 27, wherein the piston-needle assembly engages the piercing member to cause the piercing member to pierce the seal and allow the fluid formulation to flow from the reservoir through the opening and into the chamber.

29. 30. The device of claim 27, wherein the penetrating member is configured as a flexible tab having a tapered end.

30. 28. The device of claim 27, wherein the penetrating member is configured as an elongate shaft having a tapered end.

31. 24. The device of claim 23, further comprising an ingestible housing for delivery to the GI tract of the subject.

32. 24. The device of claim 23, wherein the expandable member comprises a balloon.

33. 33. The device of claim 32, further comprising a plurality of reactants disposed within the balloon to generate gas pressure within the balloon to expand the balloon within the GI lumen.

34. 34. The device of claim 33, wherein the piston-needle assembly is configured to move relative to the housing in response to the gas pressure applied against a surface of the piston-needle assembly to advance a portion of the piston-needle assembly into the GI lumen wall or into the surrounding tissue.

35. 34. The device of claim 33, wherein the membrane is made of a flexible material that allows deformation of the membrane by the gas pressure applied against an exterior surface of the membrane to expel the fluid formulation from the reservoir into the chamber.

36. 24. The device of claim 23, wherein the piston-needle assembly is configured to penetrate the GI lumen wall into the peritoneum or peritoneal cavity of the subject and expel the fluid formulation into the peritoneum or peritoneal cavity.

37. 24. The device of claim 23, wherein the reservoir defines a volume containing up to about 400 μL of fluid.

38. The device of claim 23, wherein the reservoir defines a volume containing from about 50 μL to about 300 μL of fluid.

39. 23. The device of claim 22, wherein the delivery assembly further includes a cover coupled to the housing, the cover defining a release mechanism for temporarily holding the piston-needle assembly in an axial position relative to the housing.

40. 40. The device of claim 39, wherein the cover includes a first cover portion coupled to the housing and a second cover portion coupled to the piston-needle assembly, and the release mechanism is defined by one or more tabs releasably coupled between the first cover portion and the second cover portion.

41. 41. The device of claim 40, wherein the cover further comprises one or more openings to allow gas pressure to be applied against a surface of the piston-needle assembly, and the one or more tabs are configured to disengage from at least one of the first cover portion or the second cover portion to allow the piston-needle assembly to move axially relative to the housing in response to the gas pressure reaching a threshold value.

42. The device of claim 23 , wherein the membrane extends circumferentially relative to the housing.

43. 24. The device of claim 23, wherein the housing includes one or more fill ports for filling the reservoir with the fluid formulation.

44. 24. The device of claim 23, wherein the at least one therapeutic agent is one or more selected from an immunosuppressant, a chemotherapeutic agent, a central nervous system (CNS) drug, an antidiabetic drug, an enzyme replacement therapy (ERT) drug, an antibody, a hormone, insulin, an incretin or a combination thereof, or an oligonucleotide.

45. 45. A method for delivering a fluid formulation into the GI tract lumen wall or surrounding tissue of a subject in need thereof, comprising the subject ingesting an ingestible device according to any one of claims 23 to 44.

46. 45. Use of an ingestible device according to any one of claims 23 to 44 for delivery of a fluid formulation comprising a therapeutic agent into the GI tract lumen wall or surrounding tissue of a subject in need thereof.

47. 23. A method of preparing an ingestible device for delivering a therapeutic agent into the GI tract lumen wall or surrounding tissue of a subject, comprising loading a delivery assembly according to any one of claims 1 to 22 with a fluid formulation comprising said therapeutic agent.

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