Tablets with a needle delivery system having outward-expanding mechanical action.

Abstract

The objective is to facilitate the delivery of biopharmaceuticals or other payloads. [Solution] The device may include a capsule containing an array of microneedles and a mechanical actuator. The device may be in an ingestible form for delivery to the duodenum or other target site within a subject, and the mechanical actuator can be released from the constraints of the capsule in response to stimulation or circumstances within or along the duodenum or other target site. When released from the constraints of the capsule, the mechanical actuator expands outward in a direction away from the central longitudinal axis of the mechanical actuator (for example, in response to a bias provided by the flexible elastic material of the mechanical actuator), and the array of microneedles can be driven to penetrate engagement with the inner layer of the duodenum or other target site. Penetration engagement can facilitate the delivery of biopharmaceuticals or other payloads via the microneedles.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 058,842, filed Jul. 30, 2020, which is hereby incorporated by reference in its entirety.

[0002] The present disclosure generally relates to a system for delivering a drug or other payload into a subject, and more particularly, but not necessarily limited thereto, to an ingestible tablet containing a needle delivery system operable to deliver a payload to a portion of the inner layer of the subject's gastrointestinal tract.

Background Art

[0003] Various compounds, such as biotherapeutics (including, for example, peptides, proteins, antibodies, and nucleic acids), have not been effective for oral delivery because they are at least 100 - fold larger compared to the size limits recognized for orally deliverable drugs. For example, while a biotherapeutic can be about 150 kilodaltons (kDa) in size, an orally deliverable drug can be about 0.5 kDa in size. Biotherapeutics offer greater efficacy and specificity compared to conventional small - molecule therapeutics that can be delivered and absorbed orally during the digestive process, but often have challenges in drug delivery. In essence, due to the large size of these biotherapeutics, frequent delivery by needle injection, such as with a handheld syringe or an intravenous catheter commonly referred to as an IV, has conventionally been necessary. However, injection or infusion can be a factor in patient compliance issues with taking medications, high administration costs by trained medical staff, contamination by injection needles, needle phobia, and an increased risk of systemic infection.

Summary of the Invention

[0004] Various embodiments of the present disclosure utilize outwardly expanding mechanical action to drive a needle into the inner lining of a gastrointestinal tract or other body lumen, and relate to tablets or capsules, for example, that contain a compact needle delivery system to facilitate the delivery of a therapeutic agent or other payload by such engagement within the body of the subject.

[0005] In one embodiment, the system includes a capsule. The capsule includes a shell having an inner surface that defines the internal volume of the capsule. The shell also has an outer surface sized to pass through a lumen defined by the inner lining of the digestive tract. The system may also include a carrier sized to fit within the internal volume of the capsule and supporting an array of microneedles. Furthermore, the system may also include a mechanical actuator operable to move the carrier outward in order for the microneedles to penetrate the inner lining of the digestive tract. The mechanical actuator includes a foldable biasing member, which includes a first end and a second end. The foldable biasing member includes a flexible elastic material such that the first and second ends are foldable toward each other and that it is flexible enough to move from an expanded state toward a contracted state in which the mechanical actuator fits within the internal volume of the capsule. The flexible elastic material may further have elasticity that biases the first and second ends toward each other to move from the contracted state toward the expanded state and moves the carrier outward as the mechanical actuator overcomes or circumvents constraints provided by the capsule. The mechanical actuator may also include a holder hinged to the first end of the biasing member. The holder may include a support surface for supporting a carrier that supports the array of microneedles.

[0006] In another embodiment, the system includes a capsule. The capsule includes a shell having a first shell portion, a second shell portion, and an articulation that detachably attaches the first shell portion to the second shell portion. The capsule also includes an inner surface that is at least partially defined by the first and second shell portions and defines the internal volume of the capsule. Furthermore, the capsule includes an outer surface that is at least partially defined by the first and second shell portions and sized to pass through a lumen defined by the inner lining of the digestive tract. The system may also include a carrier that is sized to fit within the internal volume of the capsule and supports an array of microneedles. Furthermore, the system may include a launcher that is operable when overcoming or circumventing constraints provided by the articulation and is operable to drive the first and second shell portions away from the carrier and expose the array of microneedles.

[0007] In further embodiments, the system includes a mechanical actuator configured for microneedle delivery. The mechanical actuator includes a foldable biasing member including a first end and a second end. The foldable biasing member may include a flexible elastic material having flexibility such that the first and second ends are foldable toward each other and can move from an expanded state to a contracted state that fits into a volume sized to fit into a capsule that the mechanical actuator can ingest. The flexible elastic material may further have elasticity that biases the first and second ends toward each other to move toward the contracted state to the expanded state. The mechanical actuator may also include a holder hinged to the first end of the biasing member. The holder may include a support surface configured to support a carrier that supports an array of microneedles. The support surface may be configured to support the carrier moving outward in response to the movement toward the contracted state to the expanded state, in order to deploy the microneedles.

[0008] In yet another embodiment, the device includes a capsule containing an array of microneedles and a launcher. The device is in an ingestible form for delivery to the duodenum of a target, and in response to stimulation or circumstances within or along the duodenum, releases a first shell portion and a second shell portion of the capsule from each other. The launcher drives the released first and second shell portions apart from each other, exposing the array of microneedles to a position for achieving penetrating engagement with the inner lining of the duodenum, caused by peristaltic contractions of the inner lining of the duodenum around the exposed array of microneedles. The penetrating engagement facilitates the delivery of the payload via the microneedles.

[0009] In further embodiments, the device includes a capsule containing an array of microneedles and a mechanical actuator. The device is in an ingestible form for delivery to the duodenum of a target, and in response to stimulation or circumstances within or along the duodenum, the mechanical actuator is released from the constraints of the capsule. Upon release from the constraints of the capsule, the mechanical actuator expands outward in a direction away from its central longitudinal axis, driving the array of microneedles to penetrate and engage with the inner lining of the duodenum. This penetration engagement facilitates the delivery of the payload via the microneedles.

[0010] In another embodiment, the system includes a capsule. The capsule includes a shell having an inner surface that defines the internal volume of the capsule. The shell also has an outer surface sized to pass through a lumen defined by the inner lining of the digestive tract. The system also includes a carrier sized to fit within the internal volume of the capsule and supporting an array of microneedles. Furthermore, the system includes a mechanical actuator operable to move the carrier outward in order to allow the microneedles to penetrate the inner lining of the digestive tract. The mechanical actuator includes a flexible elastic material having flexibility that allows the mechanical actuator to contract away from an expanded state toward a contracted state toward which the mechanical actuator fits within the internal volume of the capsule. The flexible elastic material biases the mechanical actuator to expand outward from the contracted state toward an expanded state and further has elasticity that moves the carrier outward as the mechanical actuator overcomes or circumvents constraints provided by the capsule.

[0011] Further embodiments may provide a method for treating a subject with a drug or biotherapy agent. This method may include administering a device, such as the one described above, to the subject, which may contain a drug or biotherapy payload.

[0012] In yet another embodiment, a method for fabrication can be provided. The method may include forming an assembly by connecting an array of microneedles to a mechanical actuator that is expandable outward from a central longitudinal axis. The method may further include placing the assembly within a capsule having a first state in which the capsule restricts the mechanical actuator from expanding. The capsule can be reconfigured at a target site within the object to a second state in which the constraint by the capsule is released and the mechanical actuator becomes expandable to drive the array of microneedles to engage with tissue at the target site.

[0013] These exemplary embodiments are not intended to limit or define the scope of this disclosure, but are mentioned to provide examples for the purpose of understanding it. The exemplary embodiments are described in the “Modes for Carrying Out the Invention” section, which provides further explanation. The advantages provided by the various embodiments can be further understood by examining this specification. [Brief explanation of the drawing]

[0014] The accompanying drawings incorporated herein and constituting part thereof illustrate one or more specific embodiments and serve to illustrate the principles and implementation of those specific embodiments, along with descriptions of the embodiments.

[0015] [Figure 1] Figure 1 shows a condensed, ready-to-use end view of a system for delivering therapeutic agents or other payloads inside the body, according to a specific embodiment of the present disclosure.

[0016] [Figure 2] Figure 2 shows an extended, unfolded end view of the system of Figure 1 according to a specific embodiment of the present disclosure.

[0017] [Figure 3] Figure 3 shows a retracted, ready-to-use perspective view of a tubular actuator in a particular embodiment of the present disclosure, which may be used in conjunction with the system of Figure 1.

[0018] [Figure 4] Figure 4 shows an extended, unfolded perspective view of the tubular actuator of Figure 3, according to a specific embodiment of the present disclosure.

[0019] [Figure 5] Figure 5 shows a retracted, ready-to-use end view of the tubular actuator shown in Figures 3 and 4, according to a specific embodiment of the present disclosure.

[0020] [Figure 6]FIG. 6 shows an end view of the expanded deployed state of the tubular actuator of FIGS. 3-5, according to a particular embodiment of the present disclosure.

[0021] [Figure 7] FIG. 7 shows a perspective view of an expanded, deployed state of an actuator with a hinged side column that can be used with the system of FIG. 1, according to a particular embodiment of the present disclosure.

[0022] [Figure 8] FIG. 8 shows an end view of the expanded, deployed state of the actuator of FIG. 7, according to a particular embodiment of the present disclosure.

[0023] [Figure 9] FIG. 9 shows an end view of an intermediate state of the actuators of FIGS. 7 and 8 between the contracted state and the deployed state, according to a particular embodiment of the present disclosure.

[0024] [Figure 10] FIG. 10 shows an end view of the contracted, ready state of the actuators of FIGS. 7-9, according to a particular embodiment of the present disclosure.

[0025] [Figure 11] FIG. 11 shows a perspective view of a contracted, ready state of a coiled actuator that can be used with the system of FIG. 1, according to a particular embodiment of the present disclosure.

[0026] [Figure 12] FIG. 12 shows an end view of the contracted, ready state of the coiled actuator of FIG. 11, according to a particular embodiment of the present disclosure.

[0027] [Figure 13] FIG. 13 shows an end view of the expanded, deployed state of the coiled actuators of FIGS. 11 and 12, according to a particular embodiment of the present disclosure.

[0028] [Figure 14A]Figure 14A shows an extended, unfolded perspective view of an actuator with a curved arm, which may be used in conjunction with the system of Figure 1, according to a particular embodiment of the present disclosure.

[0029] [Figure 14B] Figure 14B shows a retracted, ready-to-use end view of the actuator shown in Figure 14A, according to a particular embodiment of the present disclosure.

[0030] [Figure 15] Figure 15 shows a retracted, ready-to-use side view of an actuator with a double-hinged arm, which may be used in conjunction with the system of Figure 1, according to a particular embodiment of the present disclosure.

[0031] [Figure 16] Figure 16 shows an extended, unfolded side view of the actuator of Figure 15 according to a particular embodiment of the present disclosure.

[0032] [Figure 17] Figure 17 is a side perspective view showing a portion of a microneedle array that may be used in the system of Figure 1, according to a particular embodiment of the present disclosure.

[0033] [Figure 18] Figure 18 is a flowchart illustrating an exemplary manufacturing process relating to a specific embodiment of the present disclosure.

[0034] [Figure 19] Figure 19 shows an example of the movement of a device used on a target, according to a specific embodiment of the present disclosure.

[0035] [Figure 20] Figure 20 shows a retracted, ready-to-use perspective view of an actuator with a foldable biasing member, which may be used in conjunction with the system of Figure 1, according to a particular embodiment of the present disclosure.

[0036] [Figure 21]Figure 21 shows an extended, unfolded perspective view of the actuator of Figure 20 according to a specific embodiment of the present disclosure.

[0037] [Figure 22] Figure 22 shows an exploded assembly of the actuators shown in Figures 20 and 21, relating to a specific embodiment of the present disclosure.

[0038] [Figure 23] Figure 23 shows a partial cross-sectional end view of the actuators shown in Figures 20-22, relating to a specific embodiment of the present disclosure.

[0039] [Figure 24] Figure 24 shows an extended, unfolded perspective view of an actuator with an additional foldable biasing member according to a particular embodiment of the present disclosure.

[0040] [Figure 25] Figure 25 shows a retracted, ready-to-use perspective view of the actuator of Figure 24 according to a specific embodiment of the present disclosure.

[0041] [Figure 26] Figure 26 shows an extended, unfolded perspective view of an actuator with a holder mounted by a central hinge, according to a particular embodiment of the present disclosure.

[0042] [Figure 27] Figure 27 shows a retracted, ready-to-use perspective view of the actuator of Figure 26 according to a specific embodiment of the present disclosure.

[0043] [Figure 28] Figure 28 shows an exploded assembly of an actuator having a capsule shell portion that can be deployed relative to a core, according to a particular embodiment of the present disclosure.

[0044] [Figure 29]Figure 29 shows an assembly diagram of an actuator having a leverage surface on the outside of the core, according to a particular embodiment of the present disclosure.

[0045] [Figure 30] Figure 30 shows an assembly diagram of an actuator having a leverage surface on the inside of a core, according to a particular embodiment of the present disclosure.

[0046] [Figure 31] Figure 31 shows the actuator of Figure 28 in the environment in which it is used, according to a specific embodiment of the present disclosure. [Modes for carrying out the invention]

[0047] Examples described herein are in relation to tablets or capsules containing a compact needle delivery system. Those skilled in the art will understand that the following description is illustrative and not intended to limit in any way. Hereinafter, the embodiments illustrated in the accompanying drawings will be described in detail. The same reference numerals refer to the same or similar elements and are used throughout the drawings and the following description.

[0048] It is not for express purposes to describe or explain all the conventional features of the embodiments described herein. Of course, in developing any actual implementation, many implementation-specific decisions must be made to achieve the developer's specific goals, such as compliance with application and business constraints, and it is important to understand that these specific goals will differ from implementation to implementation and from developer to developer.

[0049] In exemplary embodiments, subjects may desire to take biotherapeutic drugs or other compounds without using injection with a syringe, intravenous infusion, and the potential for discomfort or other concerns. For this purpose, users may use the device relating to this disclosure to provide a dosage. In this embodiment, the device may be provided in the form of a swallowable tablet or capsule. Inside the tablet or capsule are components that can be deployed into the body to effectively provide an internal injection, which may cause much less tissue damage and fewer systemic effects compared to external injection or infusion. As the tablet or capsule reaches the target portion of the gastrointestinal tract (such as the duodenum), the special coating of the tablet or capsule dissolves or breaks down sufficiently to allow the mechanical actuator inside the tablet to expand outward. Various options can be employed for the outwardly expanding mechanical actuator, including stent-like tubes that expand vertically or radially, rewind coils, a set of extended curved arms, a set of double-hinged arms that unfold toward a central hub and then unfold again toward a component connected to the hub, or a scissor-lift-like arrangement with a centrally hinged lateral column where the column portions are hinged toward each other, appearing upright from a compressed to an expanded state. Multiple arrays of microneedles are arranged around the mechanical actuator and driven to engage with surrounding tissue (e.g., the inner lining of the duodenal mucosa) by expanding outward. Drug dosages can be delivered to the tissue through the engaged microneedles, for example, by flowing through the microneedles if hollow, or by direct absorption if the drug is embedded in a soluble composition of the microneedles. After dose delivery, the components of the device can be biodegraded, preventing any potentially complex elements from passing the remainder of the device out of the body. Therefore, subjects may use the device to administer internal injections that are ultimately less invasive, less cumbersome, and / or more troublesome for the subject than alternatives that use external syringes or intravenous infusions.

[0050] Referring here to the drawings (which are provided for illustrative purposes and are not necessarily to a constant scale), Figures 1 and 2 show different states of system 100 for delivering a drug or other payload into the body. System 100 may include a device 101 that can be located within a lumen 102 in the body, surrounded by, or otherwise at least partially bounded by, a luminal wall 103 formed of tissue covering the lumen 102. The device 101 may include a capsule 104 or be fitted into a capsule 104. Generally, the capsule 104 provides a constraint (e.g., as shown in Figure 1) that can be overcome, avoided, or otherwise released (e.g., as shown in Figure 2) at a target location within the object, and the device 101 can expand outward and engage with tissue at the target location for delivery of a drug or other payload. In various embodiments, the device 101 may enable payload delivery without significant obstruction of the lumen 102 within the body, and / or without considerable shear force on the mucosal lining or other inner layers or luminal wall 103 of the lumen 102 within the body. In some embodiments, the device 101 may be constructed entirely from biodegradable material, making the device 101 completely biodegradable. Being biodegradable allows the device 101 to be absorbed by the body of the subject after use, so that no portion remains that needs to pass through the excrement removed from the subject; however, in some cases, at least a portion of the decomposed biodegradable material of the device 101 may be removed through excretion.

[0051] The capsule 104 (for example, Figure 1) may include a shell 106. The shell 106 may contain or be supplemented with one or more layers of similar or different compositions to alter the function of the capsule 104, such as influencing whether the capsule 104 can disassemble or otherwise release the device 101 from the constraints imposed by the capsule within the object. The shell 106 may have or be defined an outer surface 108 and an inner surface 110.

[0052] The outer surface 108 of the capsule 104 may be sized to pass through a lumen 102 inside the body. For example, the lumen 102 inside the body may correspond to a lumen having a lumen wall 103 defined by the inner lining of the digestive tract. In some embodiments, the capsule 104 may meet the criteria for classifying it as a 000 capsule known to those skilled in the art, but other standardized capsules 104 or custom-type capsules 104 may be used. The capsule 104 may be sized to facilitate function within a specific part of the body. For example, a 000-type capsule 104 may have an outer surface 108 with a total length of approximately 26.14 mm and a body diameter of 9.55 mm, these dimensions may be suitable for operation or use in a portion of the digestive tract corresponding to the duodenum (based on the human duodenum, for example, typically ranging from 25 mm when fully open to approximately 0 mm when fully closed or constricted during peristalsis). In some embodiments, the length of the capsule 104 exceeds or is approximately equal to the expected maximum diameter or other cross-sectional dimensions of the lumen 102 inside the body, so that the device 101 is preferably aligned to expand to engage with the surrounding tissue of the lumen wall 103 (for example, the device 101 has the length of the capsule 104 and the lumen 102 inside the body aligned to expand along the diameter of the device 101 and the lumen 102 inside the body).

[0053] The inner surface 110 may, for example, form the boundary of the internal volume 112 of the capsule 104, in which the device 101 and / or their respective components may be arranged, or it may be defined in other ways. The inner surface 110 may be separated from the outer surface 108 by the wall thickness, and as a result, for example, the dimensions between each part of the inner surface 110 may be reduced from the dimensions of the outer surface 108 by twice the wall thickness. In an exemplary embodiment, a capsule 104 of type 000 may have a wall thickness of 0.11 mm such that the internal volume 112 has an overall length of approximately 25.92 mm and an inner diameter of 9.33 mm.

[0054] Figure 1 shows various components of the device 101 within the capsule 104. For example, the device 101 may include at least one array 114 of microneedles 116, a carrier 118, and a mechanical actuator 120. The array 114 may be supported by the carrier 118. The mechanical actuator 120 is movable of the carrier 118 during use. For example, the mechanical actuator 120 may move the carrier 118 outward, as indicated by arrow 122, etc. Outward movement may correspond to movement away from the central axis 124 of the mechanical actuator 120. (For example, the central axis 124 in Figure 1 is shown as a point representing an axis aligned in the direction of movement in or out of the page in the figure 1.) The outward movement of the carrier 118 caused by the mechanical actuator 120 may move the microneedles 116 toward or to engage with the tissue of the luminal wall 103 of the lumen 102 in the body, such as from the position shown in Figure 1 toward or into the position shown in Figure 2.

[0055] The microneedle 116 may correspond to any preferred form of tissue-penetrating member capable of delivering the payload to the relevant tissue. In some embodiments, the microneedle 116 comprises a soluble composition containing the payload, so that, for example, the payload can be absorbed into the engaged tissue as the engaged microneedle dissolves. Additionally or alternatively, the microneedle 116 may be hollow or otherwise include a passage through which the payload can flow for delivery.

[0056] The microneedles 116 can be suitably sized and positioned for their respective functions. For example, the microneedles 116 can be "micro" in the sense that they can be small enough to mate with other components of the device 101 within the capsule 104. In an exemplary embodiment, the microneedles 116 may have a length of about 1.5 mm, and as a result, when the microneedles 116 are supplied onto opposing sides within the capsule 104, there may be a space of about 3 mm in diameter for the capsule 104, leaving about 6.33 mm of the inner diameter of about 9.33 mm available for other components within the capsule 104 of type 000.

[0057] The microneedles 116 can be distributed in any preferred manner. In some embodiments, the microneedles 116 are grouped into arrays 114 that are distributed sequentially to one another. For example, Figure 1 shows 16 arrays 114 distributed evenly around a circumference, but any other number of one or more arrays 114 may be used and distributed evenly or unevenly. Generally, the arrays 114 used may contain any number of one or more rows and / or one or more columns of microneedles 116 (or any other clusters or arrangements that may be staggered in units of rows or columns, or otherwise cannot be clearly defined). For example, Figure 1 shows an arrangement of 16 arrays 114, each visually having three rows and one column, but another exemplary arrangement may have six arrays 114, each having two rows and twelve columns, or any other preferred combination of the number of arrays, rows and columns may be used. Furthermore, a single microneedle 116 may be used for the device 101 or within each array 114, but the amount of payload that can be delivered can be increased by increasing the number of microneedles 116 included.

[0058] In some embodiments, the microneedles 116 and / or array 114 may additionally or alternatively include certain geometric shapes or other specific physical features (such as sharpness and / or pitch) that facilitate puncture or other engagement with the respective inner layers of the luminal walls 103 of the lumen 102 within the body. Some embodiments of such features are further described with respect to Figure 17 of this specification.

[0059] The carrier 118 is shown in Figure 1 as a band that can be expanded vertically or radially under the influence of the mechanical actuator 120. However, the carrier 118 is not limited to the shape factors of the band. The carrier 118 can accommodate any suitable structure for supporting the microneedles 116.

[0060] The carrier 118 can interact with the mechanical actuator 120 in any preferred manner to move the microneedle 116 outward. In some embodiments, the carrier 118 and the mechanical actuator 120 may correspond to separate structures. For example, in Figure 1, the carrier 118 is shown to be separated from the mechanical actuator 120 and positioned around it, so that, for example, the mechanical actuator 120 can start in a state of at least partial non-contact with the carrier 118, expand outward, and then come into contact with the carrier 118, driving the carrier 118 outward together with the microneedle 116 supported by the carrier 118. Alternatively, the carrier 118 may start in a state of at least partial contact with the mechanical actuator 120. In some embodiments, the carrier 118 and the mechanical actuator 120 are coupled together to maintain contact whether the mechanical actuator 120 is expanded or contracted. In some embodiments, the carrier 118 may be a subcomponent of the mechanical actuator 120, or vice versa. For example, the carrier 118 may be integrally formed with a part of the mechanical actuator 120, or otherwise may correspond to it.

[0061] The carrier 118 can be moved using any suitable mechanical actuator 120. For this purpose, the mechanical actuators 120 are shown in Figure 1 in general terms as functional blocks indicated by dashed lines (excluded from Figure 2 for explicit purposes). Various embodiments of suitable mechanical actuators 120 are illustrated and / or described with reference to other drawings herein, and any of these mechanical actuators 120 may be used in conjunction with the arrangements illustrated and / or described with reference to Figure 1, such as replacement of the mechanical actuators 120 in Figure 1 indicated by dashed lines. For example, the mechanical actuators 120 in other drawings herein may be provided without the directly mounted microneedles 116 shown in those drawings so that they can be more easily incorporated into the arrangements illustrated and / or described with reference to Figure 1, and as a result, for example, the microneedles 116 are provided on the carrier 118 without a separate set incorporated into or on the mechanical actuator 120.

[0062] In some embodiments, the carrier 118 is a band and can move the microneedle 116 directly outward in the radial or normal direction (which may correspond to a direction perpendicular to the long axis of the lumen 102), regardless of whether the mechanical actuator 120 expands directly in the radial or normal direction. For example, the carrier 118 is a band and can effectively restrain the microneedle 116 to move directly radially / normally and / or convert or disable non-radial or non-normal components from the movement of the mechanical actuator 120.

[0063] The mechanical actuator 120 may include a suitable structure for providing outward expansion for moving the carrier 118. The structure may include or be coupled with a suitable material for providing outward expansion. For example, the mechanical actuator 120 may include a flexible elastic material. The material may have or exhibit flexibility that allows the mechanical actuator 120 to contract (e.g., away from an expanded state as shown in Figure 2 and / or towards a contracted state as shown in Figure 1). This contraction may allow the mechanical actuator 120 to fit into the internal volume 112 of the capsule. The material may further have or exhibit elasticity that biases the mechanical actuator 120 toward outward expansion (e.g., away from the state shown in Figure 1 to the state shown in Figure 2, otherwise away from the contracted state and toward an expanded state). Outward expansion allows the carrier 118 to move outward as the mechanical actuator 120 overcomes or circumvents the constraints provided by the capsule 104.

[0064] By utilizing any suitable technique, the mechanical actuator 120 can facilitate overcoming or circumventing the constraints provided by the capsule 104. In some embodiments, the capsule 104 may overcome the constraints by shattering or disintegrating at a specific target location within the object. For example, the shell 106 of the capsule 104 may include a suitable composition and / or thickness of an enteric coating to enable disintegration at the target location. The elasticity of the material of the mechanical actuator 120 may assist in the disintegration of the capsule 104. For example, the capsule 104 may disintegrate to a specific thickness or strength that can be overcome by the force provided by a pre-loaded mechanical actuator 120. In some embodiments, the capsule 104 may include components that activate or eject the mechanical actuator 120, for example, in addition to, or as an alternative to, the release of constraints by disintegration of the capsule 104. Generally, by utilizing any suitable technique, it is possible to induce the release or disengagement of constraints from the mechanical actuator 120 in response to stimulation or circumstances within or along the duodenum or other target location, including, but not limited to, the construction of the capsule 104 with some or all of a coating or other material that can cause release. For example, release may be induced in response to chemicals (such as pH), electricity, mechanical or external stimuli (such as ultrasonic energy which may be applied to affect a particular composition). Once released from the constraints provided by the capsule 104, the mechanical actuator 120 may provide the appropriate speed and / or force to drive the microneedle 116 to engage with the tissue of the lumen wall 103 of the lumen 102 in the body for payload delivery.

[0065] Figure 3 is a perspective view showing a further embodiment of a structure that may be incorporated into system 100. In some embodiments (such as Figure 3), the mechanical actuator 120 may include a collapsible tube 130. The collapsible tube 130 may be compressible toward the central longitudinal axis 124 of the mechanical actuator 120 (for example, radially or normally, which may correspond to a direction perpendicular to the long axis of the lumen 102) and expandable toward it. For example, Figures 3 and 5 show a perspective view and an end view of a ready, retracted collapsible tube 130, respectively, while Figures 4 and 6 show a perspective view and an end view of an expanded, unfolded collapsible tube 130, respectively.

[0066] While the illustration shows the microneedle 116 supported by a carrier 118 separately attached to the folding tube 130, other arrangements are also possible, including, but not limited to, arrangements in which the microneedle 116 and / or carrier 118 are instead integrally formed, or arrangements in which the carrier 118 corresponds to a band or other separate structure as described with respect to Figures 1 and 2.

[0067] As is most evident in Figure 4, the collapsible tube 130 may be formed from a network of interconnected flexible members 132. The members 132 may be arranged in the form of a grid or lace. The spacing between the members 132 may be greater in the expanded state than in the contracted state. For example, windows 134 may be formed between each member 132, and each window 134 may represent a smaller cross-sectional opening in the contracted state compared to the expanded state. In some embodiments, the members 132 and / or windows 134 may be compressed along the perimeter of the collapsible tube 130. For example, a member 132 may be compressed into a space defined by a window 134. In some embodiments (for example, as is most evident when comparing Figures 5 and 6), the tube 130 may be shown to have a smaller circumference when compressed than when expanded, rather than folding in such a way that, for example, a portion protrudes inward from the outer circumference of the collapsible tube 130. In some embodiments, the overall length of the collapsible tube is substantially the same in both the expanded and contracted states.

[0068] Member 132 may be formed from a flexible elastic material. For example, the material may provide sufficient flexibility to allow the collapsible tube 130 to compress from an expanded state to a compressed state, and the material may provide sufficient elasticity to bias the material away from a compressed state towards an expanded state, for example, to drive the microneedles 116 outward for tissue engagement. In some embodiments, member 132 is made from a biodegradable material (e.g., biodegradable within the digestive tract or a particular target portion thereof). In some embodiments, member 132 is constructed from a material suitable for constructing the collapsible tube 130 by 3D printing or other specific fabrication techniques. Some preferred embodiments of materials for member 132 may include stereophotonic (SLA) 3D printed durable resin, gelatin paper or sheet, rice paper or sheet, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers.

[0069] The collapsible tube 130, when in use, provides a substantially through-passage through the center in its expanded state, and thus can prevent or avoid complete obstruction of the lumen of the duodenum or other related body cavities 102. Furthermore, the collapsible tube 130 can provide normal outward or radial outward movement of the microneedle 116 into the inner layer of the luminal wall 103 of the body lumen 102, in a direction perpendicular to the long axis of the lumen, in order to reduce or avoid shear forces that may occur if, for example, the mechanical actuator 120 is instead provided with several tangentially oriented components in addition to radially or vertically oriented components.

[0070] Figure 7 is a perspective view showing further embodiments of structures that may be incorporated into system 100. In some embodiments (such as Figure 7), the mechanical actuator 120 may include a hinged column 138 (identified individually by subscripts A, B, and C). The hinged ability of the column 138 may allow the mechanical actuator 120 to be compressible toward the central longitudinal axis 124 of the mechanical actuator 120 (for example, radially or normally, which may correspond to a direction perpendicular to the long axis of the lumen 102) and expand away from it. For example, if Figures 7 and 8 show a perspective view and an end view of the hinged column 138 in an expanded, unfolded state, respectively, Figure 10 shows a perspective end view of the corresponding ready, retracted state, while Figure 9 shows an end view of an intermediate state between the retracted and expanded states.

[0071] As can be best understood with respect to Figure 7, the column 138 may form part of the body 140 of the mechanical actuator 120. The body 140 may include the column 138 and the crossbeams 142 (e.g., an upper crossbeam 142A and a lower crossbeam 142B).

[0072] The microneedle 116 is shown to be supported by a carrier 118 that is integrally formed with the crossbeam 142 of the main body 140, but other arrangements are also possible, including, but not limited to, arrangements in which the microneedle 116 and / or carrier 118 are instead mounted integrally and separately, or arrangements in which the carrier 118 corresponds to a band or other separate structure as described with respect to Figures 1 and 2.

[0073] The main body 140 may be, for example, roughly rectangular. The main body 140 may define corners 144, such as the upper left corner 144A, the upper right corner 144B, the lower left corner 144C, and the lower right corner 144D, as shown in Figure 7. The column 138 may be positioned laterally relative to the main body 140 and may therefore be alternatively referred to as a lateral column. The upper cross beam 142A and the lower cross beam 142B may be joined by the column 138, such as at the corners 144 of the main body 140.

[0074] Each column 138 may have its own hinge 146 (identified individually by subscripts A, B, and C). The hinge 146 may be positioned toward the center of the column 138 and therefore may be alternatively referred to as a central hinge. In some embodiments, the hinge 146 may correspond to a portion of the column 138 with a reduced cross-section compared to other parts of the column 138, but the hinge 146 may correspond to any preferred structure to facilitate bending or flexing of the column 138 around the hinge 146.

[0075] The columns 138 and / or other parts of the main body 140 may be formed from a suitable material. In some embodiments, the material is a flexible elastic material (e.g., having enough flexibility to allow it to be compressed from an expanded state to a compressed state in order to drive the microneedles 116 outward for tissue engagement, and further having enough elasticity to bias the material to expand from a compressed state toward an expanded state). In some embodiments, the material is a biodegradable material (e.g., biodegradable in the digestive tract) and / or suitable for construction by 3D printing or other specific fabrication techniques. Some examples of suitable materials may include SLA, 3D printed durable resins, gelatin paper or sheets, rice paper or sheets, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers.

[0076] The hinges 146 can facilitate reconfiguration between a contracted state (e.g., Figure 10) and an extended state (e.g., Figure 7). In the extended state (as shown in Figures 7 and 8), the hinges 146 of each column 138 can be aligned with (e.g., positioned below or above) the respective ends of the crossbeam 142 that are directly connected to the column 138. For example, the hinge 146A of the left column 138A in the extended state can be aligned and positioned below the upper left corner 144A and above the lower left corner 144C. During the transition from the extended state to the contracted state, the hinges 146 can move out of such alignment, for example, by moving toward each other as the hinges 146 bend. In some embodiments, when each hinge 146 shifts between the contracted and extended states, it moves from below or above one end of the upper crossbeam 142 to below or above the opposite end. For example, in contrast to the aforementioned position of the hinge 146A of the left column 138A in the extended position (e.g., Figure 7), the left column 138A in the retracted position (e.g., Figure 10) may be aligned (e.g., positioned below or above) each end of the crossbeam 142 that is not directly connected to column 138 (e.g., below the upper right corner 144B and above the lower right corner 144D).

[0077] The hinges 146 of different columns 138 may pass each other when they shift between contracted and expanded states during operation. For example, as is most readily apparent in Figure 9, the hinge 146A of the left column 138A passes the hinge 146B of the right column 138B when it moves to the right (e.g., as illustrated by arrow 148A) and the hinge 146B of the right column 138B moves to the left instead (e.g., as illustrated by arrow 148B). The movement of the columns 138 may cause the upper crossbeam 142A and the bottom crossbeam 142B to move toward each other (as illustrated by arrow 148C), this may be caused by, or otherwise occur simultaneously with.

[0078] Various parts of the main body 140 may be of approximately equal length to facilitate the contraction of the main body 140 into stacking and / or nesting arrangements. For example, each of the crossbeams 142 and the parts of the columns 138 on either side of the hinge 146 may be of approximately equal length. By utilizing approximately equal lengths, as can be best recognized by referring to Figure 10, a compact arrangement may be facilitated in which each part fits within a predetermined length suitable for mating into the capsule 104.

[0079] The tension member 150 may be mounted between multiple columns 138. The tension member 150 may be formed from any suitable material for applying biasing force. A preferred embodiment may include a silicone tube, but any other type of material and / or form with suitable properties may be utilized. In some embodiments, the tension member 150 is connected to one or more of the hinges 146. When in use, the tension member 150 may provide a force to bias the mechanical actuator 120 toward the extended state. In the retracted state of the device 101, the tension member 150 may be stretched more than in the extended state. For example, the stretched length of the tension member 150 between anchor points 152 in the retracted state of the device 101 (e.g., Figure 10) may be greater than the length of the tension member 150 between the same anchor points once the device 101 is moved toward the extended state (e.g., Figure 8). In some embodiments, the anchor points 152 may correspond to surfaces that face each other in the extended configuration and face away from each other in the retracted configuration. Although the anchor point 152 in Figure 8 is shown located at the hinge 146, any other suitable location along the column 138 may be utilized. The tension member 150 may increase the amount of force available from the tension member 150 due to preload in order to at least partially surround one or more of the columns 138 and bias them toward the expanded state during the shift from the expanded state to the contracted state. The tension member 150 may continue to apply some force to the column 138 in the expanded state. Thus, although the column 138 is shown completely upright in the expanded state (e.g., Figure 8), in some embodiments the expanded column 138 may exhibit some degree of inward bending or flexing as a result of the tension member 150.

[0080] Any preferred number of columns 138 can be utilized. In some embodiments, different numbers of columns 138 may be arranged on opposing lateral sides. For example, in Figure 7, one column 138A is shown on the left side, while a pair of columns 138B and 138C are shown on the right side. Slots 154 may be defined between adjacent columns, such as between a pair of columns 138B and 138C. As illustrated by arrow 156, slots 154 may be sized to allow movement through the column 138 from the opposite side during a shift between a contracted state and an expanded state. Furthermore, slots 154 may be sized to allow a tension member 150 to pass through, at least partially. In some embodiments, including two or more single columns 138 on at least one lateral side may provide greater dimensional stability and / or reduce the risk of unintended twisting compared to using only a single column 138 on each side.

[0081] The main body 140, when in use, provides a substantially through-passage in its expanded state (for example, with minimal obstruction from passages subdivided by the tension member 150), and thus can prevent or avoid complete obstruction of the lumen of the duodenum or other related internal lumen 102. Furthermore, the main body 140 can provide substantially linear outward movement of the microneedle 116, thereby engaging perpendicularly with the inner layer of the luminal wall 103 of the internal lumen 102, reducing or avoiding shear forces that might occur if the mechanical actuator 120 were instead provided with several tangentially oriented components in addition to the linear outward-facing components (such as those oriented radially or normally, which may correspond to directions perpendicular to the long axis of the lumen 102).

[0082] Figure 11 is a perspective view showing a further embodiment of a structure that may be incorporated into system 100. In some embodiments (such as Figure 11), the mechanical actuator 120 may include a coil 160. The coil 160 is compressible toward the central longitudinal axis 124 of the mechanical actuator 120 (for example, radially or normally, which may correspond to a direction perpendicular to the long axis of the lumen 102) and expandable toward it. For example, if Figures 11 and 12 show a perspective view and an end view of the ready, retracted coil 160, respectively, then Figure 13 shows a corresponding end view of the expanded, unfolded coil 160.

[0083] As can be best understood with respect to Figure 7, the coil 160 may include a plurality of overlapping rotating parts 162. For example, in Figure 7, a total of three rotating parts 162A, 162B, and 162C are visible in the lower half of the coil 160, while a total of two rotating parts 162A and 162B are visible in the upper half of the coil 160. The coil 160 is not limited to the number of rotating parts 162 shown, but may include any preferred number of rotating parts 162 to provide a suitable basis for unwinding the coil and expanding outward in order to drive the microneedle 116 into the inner layer of the luminal wall 103 of the lumen 102 in the body.

[0084] The coil 160 may be formed from a suitable material. In some embodiments, the material is a flexible elastic material (e.g., having enough flexibility to allow it to be compressed from an expanded state to a compressed state in order to drive the microneedles 116 outward for tissue engagement, and further having enough elasticity to bias the material to expand away from the compressed state toward an expanded state). In some embodiments, the material is a biodegradable material (e.g., biodegradable in the digestive tract) and / or suitable for construction by 3D printing or other specific fabrication techniques. Some examples of suitable materials may include SLA, 3D printed durable resin, gelatin paper or sheet, rice paper or sheet, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers.

[0085] The coil 160 can be easily reconfigured between a contracted state (e.g., Figure 12) and an expanded state (e.g., Figure 13). For example, the rotating portion 162 of the coil 160 can be wound more tightly (and / or more) in the contracted state (e.g., Figure 12) than in the expanded state (e.g., Figure 13). The tightness of the winding allows the coil 160 to be pre-positioned to unwind when released from constraints, driving the microneedles 116 outward.

[0086] The microneedle 116 is illustrated to be supported by a carrier 118 separately attached to the coil 160, but other arrangements are also possible, including, but not limited to, arrangements in which the microneedle 116 and / or carrier 118 are instead integrally formed, or arrangements in which the carrier 118 corresponds to a band or other separate structure as described with respect to Figures 1 and 2. Furthermore, although the microneedle 116 is shown positioned only on the outer surface of the coil 160 or on the outermost rotating portion 162, in some embodiments the microneedle 116 may be positioned additionally or alternatively on the inner surface of the coil 160 and / or on the inner rotating portion 162.

[0087] The coil 160, when in use, provides a substantially penetrating path through its center in its expanded state, and thus can prevent or avoid complete occlusion of the lumen of the duodenum or other related body lumen 102. Furthermore, the coil 160 can provide the movement of the microneedle 116, which includes several tangentially oriented components in addition to linearly outward-facing components aligned along the radial or normal direction (and thus can impart some shear force), however the amount of shear can be mitigated by adjusting the thickness of the coil 160 (for example, to give greater rigidity, which can result in a stronger force for engaging the tissue of the lumen wall 103 of the body lumen 102). Furthermore, the coil 160 may exhibit a smoother overall surface and / or fewer sharp edges than some other alternatives herein, which can further reduce the shear force. In addition, the coil 160 may present a continuous surface, which offers more options for mounting the array 114 compared to other alternatives herein. Furthermore, the shape factor of the coil 160 may facilitate the use of a fabrication process between rolls, which may be faster, more economical, and / or otherwise more beneficial compared to the fabrication processes for other alternatives specified herein.

[0088] Figure 14A is a perspective view showing further embodiments of structures that may be incorporated into system 100. In some embodiments (such as Figure 14A), the mechanical actuator 120 may include a curved arm 170 (individually identified by subscripts A, B, C, D, E, and F). The curved arm 170 is compressible toward the central longitudinal axis 124 of the mechanical actuator 120 (for example, radially or normally, which can correspond to a direction perpendicular to the long axis of the lumen 102) and expandable away from it. For example, the curved arm 170 may be curved toward each other, as shown in Figure 14A in an expanded, unfolded state, and reach a ready, retracted state (as shown in Figure 14B, etc.).

[0089] The microneedle 116 is shown to be supported by a carrier 118 integrally formed with the curved arm 170, but other arrangements are also possible, including, but not limited to, arrangements in which the microneedle 116 and / or carrier 118 are instead mounted integrally and separately, or arrangements in which the carrier 118 corresponds to a band or other separate structure as described with respect to Figures 1 and 2.

[0090] As can be best understood with respect to Figure 14A, each curved arm 170 may include a proximal end 172 and a distal end 174 opposite the proximal end 172. Each curved arm 170 may be attached to the central core 176 at the proximal end 172. For example, the proximal end 172 may be positioned in a slit within the core 176. The proximal end 172 may be additionally or alternatively fixed to the core 176 by a suitable adhesive, or otherwise joined in a swivel manner.

[0091] The curved arm 170 may define an arc between its proximal end 172 and distal end 174. The arc may change as the device shifts between a retracted state and an extended state (for example, between the states shown in Figures 14A and 14B). During operation, the curved arm 170 may be movable such that the distal end 174 rotates away from the core 176 in a helical direction as it moves from the retracted state to the extended state.

[0092] Any suitable number of curved arms 170 can be used. Thus, although six curved arms 170 are shown, a number of arms before and after the six curved arms can be used alternatively.

[0093] The curved arm 170 and / or core 176 may be formed from a suitable material and may or may not be different from each other in the material used. In some embodiments, the material is a flexible elastic material (e.g., having enough flexibility to be compressible from an expanded state to a compressed state in order to drive the microneedles 116 outward for tissue engagement, and further having enough elasticity to bias the material to expand from a compressed state toward an expanded state). In some embodiments, the material is a biodegradable material (e.g., biodegradable in the digestive tract) and / or suitable for construction by 3D printing or other specific fabrication techniques. Some embodiments of suitable materials may include SLA, 3D printed durable resin, gelatin paper or sheet, rice paper or sheet, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers. In some embodiments, the material may be provided as at least one film layer or may comprise at least one film layer. In some embodiments, the material of the curved arm 170 may be subjected to a spin coating and drying process or other suitable process that can impart a pre-stressed or pre-pressed bending structure, which can pre-position the curved arm 170 toward an equilibrium state that is more open than in the absence of such process, so that the curved arm 170 can be given a greater driving force.

[0094] The curved arm 170, in its expanded state during use (e.g., with minimal obstruction from the passage separated by the curved arm 170), provides a set of substantially penetrating passages, and thus can prevent or avoid complete obstruction of the lumen of the duodenum or other related body lumen 102. Furthermore, the curved arm 170 can provide the movement of the microneedle 116, which includes several tangentially oriented components in addition to straight, outwardly oriented components aligned radially or normally (and thus can provide some shear force), although the size of the normal components of the curved arm 170 can be larger than that provided by the coil 160 or other components described herein (e.g., can provide a stronger force for engaging with the inner layer of tissue of the lumen wall 103 of the body lumen 102).

[0095] Figure 15 is a perspective view showing further embodiments of structures that may be incorporated into system 100. In some embodiments (such as Figure 15), the mechanical actuator 120 may include a double-hinged arm 180 (identified individually by subscripts A, B, and C). The double-hinged arm 180 is compressible toward the central longitudinal axis 124 of the mechanical actuator 120 (for example, in the radial or normal direction corresponding to the direction perpendicular to the long axis of the lumen 102) and expandable toward it. For example, Figure 15 shows a side view of the double-hinged arm 180 in a ready, retracted state, while Figure 16 shows a side view of the corresponding extended, unfolded state.

[0096] The microneedle 116 is shown to be supported by a carrier 118 integrally formed with a double-hinged arm 180, but other arrangements are also possible, including, but not limited to, arrangements in which the microneedle 116 and / or carrier 118 are instead mounted integrally and separately, or arrangements in which the carrier 118 corresponds to a band or other separate structure as described with respect to Figures 1 and 2.

[0097] As can be best understood with respect to Figure 16, the double-hinged arm 180 can be extended relative to the hub 182. Any suitable number of double-hinged arms 180 can be used. Thus, although three double-hinged arms 180 are illustrated, the number of arms shown before and after these can be used alternatively.

[0098] Each of the arms 180 may have similar features, but for simplification, the various features of such arms are identified only with respect to arm 180B in Figures 16 and 17. Each double-hinged arm 180 may include a first hinge 184 and a second hinge 186, which can define each sub-part of the double-hinged arm 180. For example, a double-hinged arm may include a proximal part 188 and a distal part 190.

[0099] The first hinge 184 may connect the proximal portion 188 of the double-hinged arm 180 to the hub 182. The proximal portion 188 may extend (e.g., elongate) between the first hinge 184 and the second hinge 186.

[0100] The second hinge 186 may connect its proximal portion 188 to the distal portion 190 of the double-hinged arm 180. The distal portion 190 may extend from the second hinge 186 to the free end 192 of the double-hinged arm 180.

[0101] The first hinge 184 and / or the second hinge 186 may correspond to a portion of the double-hinged arm 180 with a reduced cross-section compared to the rest of the double-hinged arm 180, and / or to any preferred structure for facilitating the bending or flexing of the double-hinged arm 180 around the first hinge 184 and / or the second hinge 186.

[0102] The double-hinged arm 180 and / or other related components may be formed from a suitable material. In some embodiments, the material is a flexible elastic material (e.g., having enough flexibility to allow it to be compressed from an expanded state to a compressed state in order to drive the microneedles 116 outward for tissue engagement, and further having enough elasticity to bias the material to expand from a compressed state toward an expanded state). In some embodiments, the material is a biodegradable material (e.g., biodegradable in the digestive tract) and / or suitable for construction by 3D printing or other specific fabrication techniques. Some examples of suitable materials may include SLA, 3D printed durable resin, gelatin paper or sheet, rice paper or sheet, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers.

[0103] The double-hinged arm 180 can be easily reconfigured between a retracted state (e.g., Figure 15) and an extended state (e.g., Figure 16). In the retracted state (e.g., Figure 15), the proximal portion 188 of the double-hinged arm 180 may be positioned outward from the distal portion 190 of the double-hinged arm 180 with respect to the central longitudinal axis 124 of the mechanical actuator 120 (consequently, for example, the distal portion 190 is hidden from view in Figure 15). The proximal portion 188 of the double-hinged arm 180 may open away from the hub 182 when moving from the retracted state (e.g., Figure 15) to the extended state (e.g., Figure 16) (e.g., as illustrated by arrow 194). For example, the proximal portion 188 may pivot around the first hinge 184 due to the properties of the material it contains. Furthermore, the distal portion 190 of the double-hinged arm 180 may open away from the proximal portion 188 of the double-hinged arm 180 (for example, as shown by arrow 196). For example, the distal portion 190 may pivot around the second hinge 186, for example, due to the properties of the material it contains. In some embodiments, the microneedle 116 may be positioned to face inward towards the device 101 before deployment (for example, as shown by the solid line relative to the central double-hinged arm 180 in Figure 16) and to face outward from the device 101 after deployment (for example, as shown by the dashed line relative to the central double-hinged arm 180 in Figure 16). For example, the microneedle 116 may shift from a position facing inward to a position facing outward from the device as a result of deploying around the second hinge 186.

[0104] The double-hinged arm 180, in its extended state during use (e.g., with minimal obstruction from the passage separated by the double-hinged arm 180), provides a set of substantially penetrating passages, and thus can prevent or avoid complete obstruction of the lumen of the duodenum or other related body lumen 102. Furthermore, the double-hinged arm 180 can provide the movement of the microneedle 116, which includes several tangentially oriented components in addition to linearly outward-facing components aligned radially or normally (and thus can provide some shear force), although the size of the normal components of the double-hinged arm 180 can be larger than that provided by the coil 160 or other components described herein (e.g., can provide a stronger force for engaging with the inner tissue of the luminal wall 103 of the body lumen 102).

[0105] Figure 17 is a side perspective view showing an embodiment of a portion of an array 114 of microneedles 116 that may be used in system 100. A microneedle may include a base 202 and a tip 204. The tip 204 may correspond to the portion of the microneedle 116 furthest from the base 202.

[0106] Various shapes and / or other physical features can be understood in Figure 17. For example, a microneedle 116 may be characterized by a length L defined between the base 202 and the tip 204. A microneedle 116 may be further characterized by a base width W defined by the width dimension at the base 202. A microneedle 116 may have an aspect ratio corresponding to the value obtained by dividing the length L by the base width W. Sharpness S may correspond to the minimum cross-sectional size of the microneedle 116 at the tip. Pitch P may be defined as the distance between corresponding bases 202 of the microneedles. For example, pitch P may correspond to the center-to-center distance, the distance between adjacent edges, or any other relevant distance between the respective mechanisms of adjacent microneedles 116.

[0107] The preferred dimensions of the physical mechanism of the microneedle 116 can be implemented to achieve the desired engagement of the microneedle with the target tissue and release of the payload into the tissue. In some embodiments, the combination of mechanisms can mitigate the "nail bed" effect, where force is sufficiently distributed among multiple supports to prevent or reduce the effectiveness of the supports in penetrating the surface. As an example, for a microneedle 116 having a length L of about 1.5 mm, an aspect ratio of 2 to 3 and / or a pitch of 1.5 mm to 2 mm can mitigate the "nail bed" effect when engaging with duodenal tissue or other relevant inner layers of the luminal wall 103 of a lumen 102 in the body.

[0108] Additionally or alternatively, a sharpness S of 1 micron or less may enhance the ability of the microneedle 116 to sufficiently puncture the target tissue in use. In some embodiments, a sharpness S of 1 micron or less may be achieved, for example, by a three-dimensional ("3D") printing process using two-photon polymerization to generate the microneedle 116 or a suitable mold from which the microneedle 116 is generated. Achieving a sharpness S of 1 micron may be a significant improvement over the approximately 5 micron limit that may be available by other processes such as powder compression, hydraulic compression into solid needles, or electrical discharge machining (EDM).

[0109] Figure 18 is a flowchart illustrating an exemplary manufacturing process 1800 for some embodiments.

[0110] Process 1800 in operation 1810 may include forming an assembly. For example, the assembly may include an array 114 of microneedles 116 and a mechanical actuator 120. The mechanical actuator 120 is extendable outward from a central longitudinal axis 124. For example, the mechanical actuator 120 may include any structure described herein.

[0111] Operation 1810 may also include forming the microneedles 116. For example, the microneedles may be formed by the features and / or processes described with respect to Figure 17, and / or by any other combination of features and fabrication processes. The microneedles 116 may be formed by utilizing any suitable fabrication process or technique. In a non-limiting embodiment, the process may include the use of one or more 3D printing and / or molds that can impart the shape of the microneedles 116 to a suitable material. In a further example, marking between rolls may be utilized.

[0112] Operation 1810 may include connecting the microneedles 116 to the mechanical actuator 120. In some embodiments, the array 114 of the microneedles 116 is formed before it is connected to the mechanical actuator 120. For example, the array 114 may be bonded by a silicone adhesive, cyanoacrylate, or other adhesive (or otherwise bonded or mechanically connected to the mechanical actuator 120). In some embodiments, the array 114 of the microneedles 116 is mechanically connected by integrally forming the array 114 of the microneedles 116 with the material of the mechanical actuator 120. For example, the array 114 may be printed in the same printing or other fabrication process that forms the material of the mechanical actuator 120, or otherwise fabricated. In some embodiments, the array 114 is connected by the use of an intervening structure. For example, the mechanical actuator 120 may be located within an expandable band or other carrier 118 that supports the microneedle 116 (e.g., Figure 1), which may include alternatives to the mechanical actuator 120 that are fixed to or not fixed to the expandable band or other carrier 118.

[0113] Operation 1810 may also include forming a mechanical actuator 120. By this fabrication, part or all of the mechanical actuator 120 may be produced in an equilibrium state, from which the mechanical actuator 120 can be compressed to reach a contracted state (which may be provided by the capsule 104) in which it is ready to expand when released from constraint. Carriers 118 and / or arrays may be coupled with the mechanical actuator 120 before and / or after compression from the equilibrium or expanded state.

[0114] The mechanical actuator 120 can be formed using any suitable manufacturing process or technique. In some embodiments, all or at least part of the mechanical actuator may be produced by 3D printing, SLA, or other additive or subtractive manufacturing processes. In some embodiments, the material for the mechanical actuator 120 may be provided as or include at least one film layer and / or may be subjected to a spin coating and drying process or other suitable process that can impart a pre-stressed or pre-pressed structure to assist the function of the mechanical actuator 120. In some embodiments, a roll-to-roll process may be utilized. As an exemplary embodiment, in some embodiments, to produce a coil 160, the material may be provided as a sheet or film from a roll-to-roll process, wound around a mandrel, and cut into portions that can be removed from the mandrel for insertion into a capsule, with microneedles on the outermost layer.

[0115] Any suitable material or combination of materials may be used to generate and / or connect the respective elements during the fabrication of the assembly having the mechanical actuator 120 and the microneedles 116. In some embodiments, the material is a flexible elastic material (e.g., having enough flexibility to allow it to be compressed from an expanded state to a compressed state in order to drive the microneedles 116 outward for tissue engagement, and further having enough elasticity to bias the material to expand from a compressed state toward an expanded state). In some embodiments, the material is a biodegradable material (e.g., biodegradable in the digestive tract) and / or suitable for construction by 3D printing or other specific fabrication techniques. Some embodiments of suitable materials may include stereophotonic (SLA) 3D printed durable resins, gelatin paper or sheets, rice paper or sheets, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers. In some embodiments, the material may be provided as at least one film layer or may include at least one film layer. In some embodiments, the material may be produced in a pre-tensioned state, which can impart a specific bias to contribute to the transition from a contracted state to an expanded state, and may include casting foaming.

[0116] Process 1800 in operation 1820 may include placing the assembly inside the capsule 104. For example, the capsule 104 may have a first state in which the capsule 104 restricts the mechanical actuator 120 from expanding, and the capsule 104 may be reconfigurable at the target site within the object to a second state in which the constraint by the capsule 104 is released, allowing the mechanical actuator 120 to expand to drive the array of microneedles 116 114 to engage with tissue at the target site. The target site may correspond to, for example, the duodenum or other body lumen 102.

[0117] Operations 1810 and 1820 may be performed sequentially or at least partially overlap. For example, in some embodiments, forming an assembly in operation 1810 may involve inserting each component into the capsule 104 so that the assembly is formed within the capsule 104.

[0118] Figure 19 shows an example of the movement of the device 101 used on a subject 1902. For example, a device 101 manufactured relating to process 1800 and / or other disclosures herein may be used to treat a subject 1902. The device 101 may be introduced into the stomach 1906 of the subject. For example, the device 101 may be contained in a tablet or otherwise ingestible form that allows the device 101 to be swallowed and passed through the mouth 1910 and esophagus 1912 of the subject into the stomach 1906 of the subject (for example, as indicated by arrow 1908). The device 101 may pass from the stomach 1906 into the duodenum 1914 (for example, as indicated by arrow 1916). For example, while device 101 is shown in the duodenum 1914 as an example of a suitable target location for device 101's operation, the target location may alternatively include any other location in the digestive tract, such as the distal small intestine (i.e., the jejunum and ileum) 1918, the large intestine 1920, or the colon 1922. Device 101 may be activated at the target location in response to stimuli and / or conditions present within or along the target location. By activation, a microneedle 116 (not shown in the diagram of device 101 in Figure 19) may expand outward into the tissue at the target location to deliver a drug or other payload. Suitable payloads may include, for example, small molecules and biotherapeutic agents (e.g., peptides, monoclonal antibodies, and nucleic acids). In various embodiments, after or in conjunction with payload delivery, each component of the device 101 may be absorbed by the subject 1902 (for example, based on the use of biodegradable materials) and / or may be excreted from the subject 1902, for example, through the colon 1922 of the subject 1902 in other excrement.

[0119] Figure 20 is a perspective view showing further embodiments of structures that may be incorporated into system 100. In some embodiments (such as Figure 20), the mechanical actuator 120 may include a foldable biasing member 220. The folding capability of the foldable biasing member 220 allows the mechanical actuator 120 to be compressible toward the central longitudinal axis 124 of the mechanical actuator 120 (for example, radially or normally, which may correspond to a direction perpendicular to the long axis of the lumen 102) and expand away from it. For example, Figure 20 shows a perspective view of the foldable biasing member 220 in a ready, retracted state, while Figure 21 shows a perspective view of the corresponding expanded, unfolded state. Furthermore, Figure 22 shows a diagram of the disassembled assembly, and Figure 23 shows a partial cross-sectional end view along the line shown in Figure 20.

[0120] As is most evident in Figure 22, the foldable biasing member 220 can be associated with the holder 222. For example, the foldable biasing member 220 can be hinged to the holder 222.

[0121] The microneedle 116 is shown to be supported by a carrier 118 separately attached to the holder 222, but other arrangements are also possible, including, but not limited to, arrangements in which the microneedle 116 and / or carrier 118 are instead integrally formed, or arrangements in which the carrier 118 corresponds to a band or other separate structure as described with respect to Figures 1 and 2.

[0122] Referring further to Figure 22, the foldable biasing member 220 and / or holder 222 may be associated with a link mechanism 224. For example, the foldable biasing member 220 and holder 222 may be hinged together via the link mechanism 224. At one end or section, the link mechanism 224 may, for example, receive or be otherwise connectable to the foldable biasing member 220, and at another end or section, may be hinged to or otherwise connectable to the holder 222.

[0123] Any suitable hinge 225 may be utilized. For example, as shown in Figure 22, the hinge 225 includes a post 226 and a corresponding seat 228 positioned to receive the post 226 and to allow rotation of the post 226 or rotation relative to it. The illustration in Figure 22 shows the seat 228 as a hook formed within the holder 222 and the post 226 supported by the linkage 224, but other modifications may be preferred. For example, the relative positioning may be reversed such that the post 226 is supported by the holder 222 while the seat 228 is supported by the linkage mechanism 224 (similar to the arrangement in Figure 24, for example). In some embodiments, the seat 228 may correspond to a closing collar rather than an opening hook. Integral-molded hinges or other hinge interfaces may be used additionally or alternatively to connect the holder 222 to the linkage mechanism 224 and / or the folding biasing member 220.

[0124] The foldable biasing member 220, holder 222, link mechanism 224, hinge 225, and / or other related components may be formed from a suitable material. In some embodiments, at least a portion of the material is a flexible elastic material (e.g., having enough flexibility to allow compression from an expanded state to a compressed state in order to drive the microneedles 116 outward for tissue engagement, and further having enough elasticity to bias the material to expand from a compressed state toward an expanded state). In some embodiments, the material is a biodegradable material (e.g., biodegradable in the digestive tract) and / or suitable for construction by 3D printing or other specific fabrication techniques. Some examples of suitable materials may include SLA, 3D printed durable resin, gelatin paper or sheet, rice paper or sheet, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers.

[0125] In some embodiments, the materials used may include non-biodegradable materials (e.g., which may pass through excretion). In some embodiments, the material of the foldable biasing member 220 may include metals such as nitinol or related alloys. In some embodiments, superelastic nitinol may be used, which may show improved performance compared to thermosetting nitinol (e.g., which may exhibit memory). For example, superelastic nitinol can be significantly bent and strained without permanent deformation. Nitinol may allow folding into a compressed state and provide a suitable expansion force to drive the microneedles 116. Nitinol is further preferably durable to remain folded for a considerable amount of time, and to be able to hold a stressed state without exhibiting significant plastic deformation, creep, and / or other decomposition that may negatively affect performance. Furthermore, although the foldable biasing member 220 is shown as a multiple-wire morphological factor, any other suitable morphological factor, including but not limited to individual wires or bars, may be utilized. In some embodiments, sheet metal pieces may be used additionally or alternatively. Stainless steel or other materials suitable for use in springs may be used additionally or as substitutes.

[0126] Any suitable number of foldable biasing members 220, holders 222, and / or linkage mechanisms 224 can be used, and the number of each may be similar or different from one another. For example, Figure 21 shows a total of four foldable biasing members 220, two holders 222, and four linkage mechanisms 224, but one, two, three, four, or any other number can be used. Each element, if it has the same name, may have similar characteristics, but for the sake of simplification and to avoid obscuring the figure, various such characteristics are identified mainly with respect to the top left portion of such characteristics in Figure 21.

[0127] The foldable biasing member 220 may include a first end 230 and a second end 232. Due to the flexibility of the foldable biasing member 220, the first end 230 and the second end 232 can be folded toward each other, such as moving from an extended state (e.g., Figure 21) to a retracted state (e.g., Figure 20). Conversely, due to the elasticity of the foldable biasing member 220, the first end 230 and the second end 232 can be biased toward each other, such as moving from a retracted state (e.g., Figure 20) to an extended state (e.g., Figure 21).

[0128] The foldable biasing member 220 (e.g., at its end) may be received by a connecting portion 224 or otherwise covered. For example, as shown in Figure 21, the first end 230 may be received and covered within a first link mechanism 224A, while the second end 232 may be received and covered within a second link mechanism 224B. Covering both ends of the foldable biasing member 220 may prevent exposure to the sharp tip or other puncture risks as it passes through the body. For example, if the foldable biasing member 220 is formed of a non-biodegradable material, the link mechanism 224 may also be formed of a non-biodegradable material as a safety measure as it passes through the digestive tract. In some embodiments, a coating of silicone or other material may be placed around the foldable biasing member 220 (e.g., between the first link mechanism 224A and the second link mechanism 224B) to prevent exposure of the foldable biasing member 220 to metal or other materials.

[0129] As is most evident in Figure 23, the link mechanism 224 may define a channel 234. The channel 234 may be sized to receive a holder 222, a microneedle 116, and / or a carrier 118. For example, the channel 234 may have height, width, and / or depth such that such components can be at least partially fitted. The channel 234 may be sized such that the microneedle 116 is positioned so as not to come into contact with the capsule 104 when the device 101 is in a compressed state. By keeping the microneedle 116 out of contact with the capsule 104, blunting of the microneedle 116, which would otherwise reduce its effectiveness during deployment, can be prevented.

[0130] The holder 222 may include a mechanism suitable for engaging with other components. For example, as is most evident in Figure 22, the holder 222 may include a support surface 236 capable of supporting the carrier 118 and / or microneedle 116 in use. The support surface 236 is positioned to receive the separately mounted carrier 118 (e.g., by adhesive, overmolding, or other mounting techniques), but the support surface 236 may support the carrier 118 in other ways, either by being formed integrally together or by engaging with a band or other separate structure as described with respect to Figures 1 and 2.

[0131] The holder 222 can be attached to multiple other components at opposing ends or sides. For example, in Figure 22, the first or upper holder 222A is hinged on the left and right sides (which may correspond to the front and rear, for example) to the first or upper left link mechanism 224A and the third or upper right link mechanism 224C, respectively, while the second or lower holder 222B is hinged on the left and right sides to the second or lower left link mechanism 224B and the fourth or lower right link mechanism 224D, respectively. Furthermore, in Figure 22, the first foldable biasing member 220A and the second foldable biasing member 220B are shown connected to the first holder or upper holder 222A and the second holder or lower holder 222B (for example, based on connections with the first or upper left link mechanism 224A and the second or lower left link mechanism 224B), while the third foldable biasing member 220C and the fourth foldable biasing member 220D are also shown connected to both the first or upper holder 222A and the second or lower holder 222B (for example, based on connections with the third or upper right link mechanism 224C and the fourth or lower right link mechanism 224D).

[0132] The foldable biasing member 220 can be easily reconfigured between a contracted state (e.g., Figure 20) and an extended state (e.g., Figure 21) during use. For example, in the contracted state (e.g., Figure 20), the foldable biasing member 220 may be in a folded state (e.g., approximating a curve or arc). In the folded state, the foldable biasing member 220 may be positioned such that opposing ends (e.g., a first end 230 and a second end 232) are aligned (e.g., positioned below or above each other). In the contracted state (e.g., Figure 20), the foldable biasing members 220 from opposing sides of the device 101 may form overlapping loops, while in the extended state (e.g., Figure 21), the foldable biasing members 220 from opposing sides of the device 101 may be positioned spaced apart from each other without overlapping. Furthermore, in the retracted state (for example, Figure 20), the holder 222 may be at least partially positioned within the channel 234 of the link mechanism 224.

[0133] The foldable biasing member 220 may expand outward, such as becoming at least partially linear, when released from constraint, for example, to move away from the folded state (e.g., from the state shown in Figure 20 to the state shown in Figure 21). In response to the outward expansion, the adjacent or aligned link mechanisms 224 facing each other may move away from each other (as can be understood in Figure 21, for example, by the first link mechanism 224A and the second link mechanism 224B which are displaced away from each other from the starting position shown in Figure 20).

[0134] Furthermore, rotation may occur with respect to the hinge 225 (for example, around the post 226 and sheet 228) in response to outward expansion. Rotation around the hinge 225 may cause the linkage mechanism 224A to reorient so that the channel 234 moves at least partially away from the carrier 118, exposing the microneedle 116. Also, in response to outward expansion, the microneedle 116 may move outward to engage with the surrounding tissue.

[0135] Additional mechanisms may be included to control and / or limit deployment. As is most evident in Figure 22, the holder 222 may include a removable mounting surface 238. The removable mounting surface 238 may be located on the underside of the holder 222 and / or opposite the support surface 236. For example, as shown in Figure 22, the removable mounting surface 238 is located on the underside of a protruding stem extending away from the support surface 236. As is most evident in Figure 21, the removable mounting surfaces 238A and 238B of opposing holders 222A and 222B may face each other in a spaced-out relationship when in use in the extended state. In contrast, as is most evident in Figure 20, in the retracted state, the removable mounting surfaces 238A and 238B of opposing holders 222A and 222B may contact and / or engage with each other. For example, the removable mounting surfaces 238A and 238B may be removablely attached by a releaseable biodegradable adhesive or other feature in response to conditions encountered within the lumen 102. The engagement of the opposing releaseable mounting surfaces 238A and 238B may hold the opposing holders 222A and 222B aligned with each other, preventing one side (e.g., the left or right side in Figure 20) from expanding in front of the other during reconstruction from a contracted to an expanded state. For example, by releasing the opposing releaseable mounting surfaces 238A and 238B (e.g., in response to conditions within the lumen 102), the central portions of the opposing holders 222A and 222B may move away from each other for deployment, allowing the opposing holders 222A and 222B to remain symmetrically or parallel during deployment. Such symmetrical or parallel orientations may facilitate effective engagement by all or a substantial portion of the microneedles 116 on the carrier 118, and angled deployment may be avoided, which would allow some selected microneedles 116 to be positioned only at the ends of the holder 222 in positions suitable for engagement with the surrounding tissue. In addition, or alternatively, opposing holders 222A and 222B may be held in a parallel orientation before deployment by a releasable collar or clamp around the outside of the assembly, in addition to or instead of a releasable mounting surface 238 on the inside of the assembly.

[0136] In some embodiments, deployment may be controlled and / or constrained by a hinge stopper 240. For example, as is most evident in Figure 22, the hinge stopper 240 may include a hinge stopper 242 on the holder 222 and / or a hinge stopper 244 on the link mechanism 224. The hinge stopper 242 on the holder 222 and / or the hinge stopper 244 on the link mechanism 224 may be positioned to contact or block each other and / or other parts during the relative rotation of deployment. The hinge stopper may, in use, prevent over-rotation of the holder 222 beyond a predetermined limit relative to the link mechanism 224 and / or the folding biasing member 220. By preventing over-rotation, it is possible to prevent over-expansion, transposition, and / or other misaligned or uneven operation of the deploying microneedle 116. In an exemplary embodiment, the hinge stopper 240 may prevent rotation of an angle greater than 80° between the holder 222 and the link mechanism 224, but 60°, 65°, 70°, 75°, 80°, 85°, 90°, 95°, 100°, or other maximum angles may also be utilized.

[0137] The foldable biasing member 220, when in use, in its expanded state (e.g., between or around the foldable biasing member 220), may provide a substantially through-passage and / or bypass passage through the center, thus preventing or avoiding complete occlusion of the lumen of the duodenum or other related body lumen 102. Furthermore, the foldable biasing member 220 may provide substantially linear outward movement of the microneedle 116, thereby engaging perpendicularly with the inner layer of the lumen wall 103 of the body lumen 102, reducing or avoiding shear forces that might occur if the mechanical actuator 120 were instead provided with several tangentially oriented components in addition to the linear outward-facing components (such as those oriented along the radial or normal direction, which may correspond to a direction perpendicular to the long axis of the lumen 102).

[0138] Figure 24 is a perspective view showing a further embodiment of a structure that may be incorporated into system 100. Figure 24 shows another embodiment in which the mechanical actuator 120 may include a foldable biasing member 220. Various features of Figure 24 may correspond to the features described above with respect to Figures 20-23, and for simplicity, such features will not be repeated in their description. Figure 24 shows a perspective view of the extended, unfolded foldable biasing member 220, and Figure 25 shows a perspective view of the corresponding ready, retracted state.

[0139] Figure 24 shows an embodiment in which three or more holders 222 are used. For example, Figure 24 includes three holders 222. Each holder 222 is shown hinged to an opposing side or end. For example, each holder 222 is shown to be positioned to engage with a pair of respective link mechanisms 224. The three link mechanisms 224 are shown at each end of the device 101 for a total of six link mechanisms 224. In contrast to the arrangement in Figure 21, which includes two foldable biasing members 220, both extending from one link mechanism 224 and both housed within a single other link mechanism 224, the arrangement in Figure 24 includes a foldable biasing member 220 extending from one link mechanism 224 to multiple other link mechanisms 224. The foldable biasing member 220 may extend from a single link mechanism 224 to multiple laterally adjacent link mechanisms 224. For example, on the right side of Figure 24, one foldable biasing member 220 extends from the upper link mechanism 224 to the left link mechanism 224, which is positioned laterally adjacent in a counterclockwise direction, while another foldable biasing member 220 extends from the upper link mechanism 224 to the right link mechanism 224, which is positioned laterally adjacent in a clockwise direction.

[0140] Figure 24 shows an embodiment in which the hinge 225 is provided with a different shape factor than those shown in Figures 20-23. For example, the hinge 225 in Figure 24 includes a post 226 supported by a holder 222 and a seat 228 supported by a link mechanism 224, but other arrangements may utilize other hinged interface options described herein.

[0141] Figure 24 further illustrates an embodiment in which the hinge stopper 240 is provided with a different shape factor than those shown in Figures 20-23. For example, the hinge stopper 240 of Figure 24 on the holder 222 includes one hinge stopper surface 242 formed as a flange or extension that engages with another hinge stopper surface 244 on the link mechanism 224 during the unfolding rotation to prevent or reduce over-rotation.

[0142] Figure 26 is a perspective view showing a further embodiment of a structure that may be incorporated into system 100. Figure 26 shows another embodiment in which the mechanical actuator 120 may include a foldable biasing member 220. Various features of Figure 26 may correspond to the features described above with respect to Figures 20-23 and / or Figures 24 and 25, and for the sake of simplification, such descriptions will not be repeated. Figure 26 shows a perspective view of the foldable biasing member 220 in an extended, unfolded state, and Figure 27 shows a perspective view of the corresponding ready, retracted state.

[0143] Figure 26 shows an embodiment in which the hinge 225 is connected to the central portion of the holder 222. For example, a single hinge 225 can connect the holder 222 to the rest of the apparatus 101, in contrast to the arrangements in Figures 20-23 and / or Figures 24 and 25, in which, for example, the holder 222 engages with multiple hinges 225 at opposing ends or sides. Connecting the holder 222 via a single hinge can provide the holder 222 with a degree of freedom to continue rotating during deployment, for example, so that if one end engages with the surrounding tissue, the opposite end can continue to rotate and engage with the surrounding tissue as well.

[0144] Figure 28 is a perspective view showing a further embodiment of a structure that may be incorporated into System 100 (for example, in place of and / or with other features of this specification). Apparatus 101 may include a core 250, which is deployable from capsule 104 in use.

[0145] The microneedle 116 is illustrated to be supported by a carrier 118 separately attached to the core 250, but other arrangements are possible, including but not limited to arrangements in which the microneedle 116 and / or carrier 118 are instead formed integrally.

[0146] The capsule 104 may include features that facilitate the acceptance of the core 250 within the capsule 104. For example, the capsule may include a first shell portion 252 and a second shell portion 254 that can be combined to form the capsule 104 used. The capsule 104 may include a matching profile or shape for the core 250. For example, the capsule 104 in Figure 28 is shown with three grooves 256, each sized to receive three flanges 257 defined by the core 250, but other numbers and / or sizings may also be available. The flanges 257 may, for example, provide mounting surfaces for a microneedle 116. The grooves 256 may index and / or otherwise prevent or limit rotation or other movement of the core 250 within the capsule 104 during use. The grooves 256 may be sized to accommodate the microneedle 116, for example, by providing a space in which the microneedle 116 can be positioned without contacting other parts of the capsule 104 in a manner that could otherwise lead to blunting of the microneedle before use.

[0147] The apparatus 101 may include a launcher 258. The launcher 258, shown as a spring in Figure 28, may correspond to any structure that separates the first shell portion 252 and the second shell portion 254 from each other and / or separates them from the core 250 in use. Other non-limiting embodiments may include the use of expandable material (such as a superabsorbent polymer) and / or propellants or other gas expansion. The launcher 258 may be mounted within the first shell portion 252 and / or the second shell portion 254 and / or otherwise held, allowing the core 250 to be independent of or separated from the launcher 258. In some embodiments, a portion of the launcher 258 may be additionally or alternatively held within the core 250 or connected to the core 250 and / or otherwise separated from the first shell portion 252 and / or the second shell portion 254.

[0148] The launcher 258 may interact with and / or respond to other suitable structures. In one embodiment, the core 250 may include at least one leverage surface 260. For example, in Figure 29, the leverage surface 260 is located at either end of the outside of the core 250 and provides a surface that the launcher 258 can press on during use. In Figure 29, the launcher 258 is located entirely outside the core 250.

[0149] In some embodiments, the relevant structures may be at least partially within the core 250. For example, in Figure 29, the core 250 includes an internal hollow cavity with the leverage surface 260 as its end. Springs or other structures of the launcher 258 may be positioned to extend at least partially into the core 250 to press against the leverage surface 260 in use, for example. In some embodiments, the core 250 may be entirely hollow, allowing components of the launcher 258 to abut, contact, or otherwise engage with each other through the core 250.

[0150] The first shell portion 252 and the second shell portion 254 can be detachably attached together by an articulation portion 262 (e.g., Figure 29) during use. The articulation portion 262 may extend, for example, around the periphery of the capsule 104. The articulation portion 262 may correspond to a coating or other suitable structure that can decompose or otherwise cause release in response to stimuli or conditions within or along a duodenum or other target location, such as in response to chemical (e.g., pH), electrical, mechanical, or external stimuli (e.g., ultrasonic energy which may be applied to affect a particular composition). The articulation portion 262 may provide sufficient strength to engage and hold the first shell portion 252 and the second shell portion 254 together, despite the presence of the launcher 258, before decomposition or release.

[0151] The launcher 258 can be activated or activated when overcoming or circumventing constraints provided by the joint 262. For example, the capsule 104 may, upon use, reach the duodenum or other target location and initiate disassembly and / or release. This causes the launcher 258 to guide the first shell portion 252 and the second shell portion 254 away from each other and / or drive the core 250 (e.g., shifting from a stowed state shown in either Figure 29 or Figure 30 to an deployed state shown in Figure 28). In embodiments in which the launcher 258 includes a spring, the spring may press against the leverage surface 260 to drive the first shell portion 252 and the second shell portion 254 away from each other. In embodiments in which the launcher 258 includes expandable material, fluid from the target location may enter and produce a chemical reaction that causes expansion to drive the first shell portion 252 and the second shell portion 254 away from each other.

[0152] A launcher 258, which drives the first shell portion 252 and the second shell portion 254 apart, can expose the microneedle 116 to a position suitable for penetrating the surrounding tissue. For example, referring to Figure 31, the tissue of the luminal wall 103 of the duodenum or other target location may contract around the core 250, for example, in response to peristaltic contraction. Such contraction around the core 250 may provide sufficient force to achieve penetrating engagement of the microneedle 116 into the inner layer of the duodenum or other target location. Penetrating engagement may cause the microneedle 116 to remain engaged with the tissue without a suitable release force. In various embodiments, the carrier 118 of the microneedle 116 may be attached to the core 250 by adhesive or other types of bonding, configured to release when subjected to a release force smaller than the magnitude of the release force. As a result, the carrier 118 of the microneedle 116 may detach from the core 250 and retain engagement with the tissue as the tissue contracts during peristalsis or other cycles. Maintaining engagement with the tissue can facilitate, for example, the delivery of a payload via the microneedle 116. The release force may vary depending on the arrangement of the microneedle 116 being implemented, and the release force may be adjusted based on the binding technique being used.

[0153] The core 250, launcher 258, and / or other related components may be formed from a suitable material. In some embodiments, at least a portion of the material is a flexible elastic material (e.g., having enough flexibility to compress the launcher 258 to drive the first shell portion 252 and the second shell portion 254 apart, and further having enough elasticity to bias the material toward expansion). In some embodiments, the material is a biodegradable material (e.g., biodegradable in the digestive tract) and / or suitable for construction by 3D printing or other specific fabrication techniques. Some examples of suitable materials may include SLA, 3D printed durable resin, gelatin paper or sheet, rice paper or sheet, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers. In some embodiments, the material used may include a non-biodegradable material (e.g., one that can pass through excretion). As a non-limiting example, the material may include stainless steel or other metals (such as the coil spring or other spring component for launcher 258), plastic (such as for core 250, first shell portion 252, and / or second shell portion 254), or other substances.

[0154] The above descriptions of some embodiments are presented for illustrative and explanatory purposes only and are not intended to be exhaustive or to limit this disclosure to the exact form disclosed. Numerous modifications and adaptations will be apparent to those skilled in the art without departing from the spirit and scope of this disclosure. For example, steps in order of or in number may be performed in relation to this disclosure than in the processes described herein. Furthermore, other structures may perform one or more steps of the processes described herein.

[0155] In some embodiments, an apparatus, system, or method is provided relating to one or more of the following embodiments, or to some combination of elements thereof. In some embodiments, an apparatus or system described in one or more of these embodiments can be used to perform a method described in one of the other embodiments. Furthermore, features described with respect to an apparatus or system may be implemented with respect to a method, and vice versa.

[0156] Appearance 1. A device comprising a capsule containing an array of microneedles and a mechanical actuator, the device being in an ingestionable form for delivery to the duodenum of a target, wherein, in response to stimulation or circumstances within or along the duodenum, the device releases the mechanical actuator from the constraints of the capsule, and upon release from the constraints of the capsule, the mechanical actuator expands outward in a direction away from the central longitudinal axis of the mechanical actuator, driving the array of microneedles into penetrating engagement with the inner lining of the duodenum, thereby facilitating delivery of the payload via the microneedles.

[0157] Appearance 1A. Mechanical actuators are A foldable biasing member comprising a first end and a second end, wherein the first end and the second end exhibit flexibility that allows them to fold toward each other for movement from an expanded state to a contracted state, and elasticity that biases the first end and the second end toward each other for movement from a contracted state to an expanded state, The apparatus according to embodiment 1, comprising a holder, which is hinged to the first end of a biasing member and includes a support surface for supporting an array of microneedles.

[0158] Appearance 2. The apparatus according to embodiment 1, wherein the apparatus is entirely formed from one or more biodegradable materials, and is so completely biodegradable that no part remains that needs to pass through the excrement removed from the object.

[0159] Appearance 3. The apparatus of embodiment 1, wherein the mechanical actuator is formed from a structure that allows it to pass through in order to avoid complete obstruction of the duodenal lumen by the mechanical actuator when the mechanical actuator is in an outwardly expanded state.

[0160] Appearance 4. Mechanical actuators are A collapsible tube that is compressible toward the central longitudinal axis of the mechanical actuator and expandable away from it, An upper crossbeam and a lower crossbeam joined by lateral columns having a central hinge, A coil having multiple overlapping rotational sections that is wound more tightly in the contracted state than in the expanded state, A hub comprising a plurality of curved arms, each attached to a central core at its proximal end and movable so as to move from a contracted state to an extended state by rotating spirally away from the core at its distal end, and a plurality of double-hinged arms, each of which (i) the proximal portion of the arm is connected to the hub The apparatus according to embodiment 1, comprising a hub including (ii) a first hinge connected to the arm, and a second hinge connecting the proximal portion of the arm to the distal portion of the arm.

[0161] Appearance 5. The apparatus according to embodiment 1, wherein an array of microneedles is arranged around a mechanical actuator and supported by an expandable band configured to expand in response to the expansion of the mechanical actuator.

[0162] Appearance 6. It is a system, It is a capsule, The inner surface that defines the internal volume of the capsule, A capsule comprising a shell having an outer surface sized to pass through a lumen defined by the inner lining of the digestive tract, The carrier is sized to fit within the internal volume of the capsule and supports the array of microneedles, allowing the microneedles to penetrate the inner lining of the digestive tract. A system comprising a mechanical actuator that is operable to move outward, and includes a flexible elastic material that allows the mechanical actuator to contract toward a contracted state, away from an extended state, toward a contracted state toward a

[0163] Appearance 6A. The mechanical actuator includes a biasing member that can fold its first end and second end toward each other, and the first end of the biasing member The system according to embodiment 6, comprising a holder that is hinged and includes a support surface for supporting an array of microneedles.

[0164] Appearance 7. The system according to embodiment 6, wherein the capsule is configured to free the mechanical actuator from the constraints of the portion of the digestive tract corresponding to the duodenum.

[0165] Appearance 8. The system according to embodiment 7, wherein the capsule is configured to break down in the duodenum to release the mechanical actuator from constraint.

[0166] Appearance 9. The system according to embodiment 6, wherein the mechanical actuator and the carrier are each configured to move outward in a direction away from the central longitudinal axis of the mechanical actuator.

[0167] Appearance 10. The system according to embodiment 6, wherein the mechanical actuator includes a collapsible tube that is compressible toward the central longitudinal axis of the mechanical actuator and expandable away from there.

[0168] Appearance 11. The system according to embodiment 10, wherein the collapsible tube is formed from a network of interconnected flexible members, the spacing between members being greater in the expanded state than in the contracted state.

[0169] Appearance 12. The system according to embodiment 6, wherein the mechanical actuator includes an upper crossbeam and a lower crossbeam joined by lateral columns having a central hinge.

[0170] Appearance 13. The system according to embodiment 12, wherein at least one of the intermediate hinges moves from below one end of the upper crossbeam to below the opposite end when shifting between a contracted state and an extended state.

[0171] Appearance 14. The system according to embodiment 12, wherein the intermediate hinges pass each other when shifting between a contracted state and an extended state.

[0172] Appearance 15. The system according to embodiment 12, wherein the lateral columns include at least one pair of columns, each of which moves between a contracted state and an expanded state, thereby defining a slot.

[0173] Appearance 16. The system according to embodiment 6, wherein the mechanical actuator includes a coil having multiple overlapping rotational portions that are wound more tightly in the contracted state than in the expanded state.

[0174] Appearance 17. The system according to embodiment 6, wherein the mechanical actuator includes a plurality of curved arms, the proximal end of which is attached to a central core and the distal end which rotates spirally away from the core so as to move from a contracted state to an extended state.

[0175] Appearance 18. The system according to embodiment 6, wherein the mechanical actuator is a hub connected to a plurality of double-hinged arms, each double-hinged arm comprising a hub including (i) a first hinge connecting the proximal portion of the double-hinged arm to the hub, and (ii) a second hinge connecting the proximal portion of the double-hinged arm to the distal portion of the double-hinged arm.

[0176] Appearance 19. The system according to embodiment 18, wherein, in the retracted state, the proximal portion of the double-hinged arm is positioned outward with respect to the central longitudinal axis of the mechanical actuator, relative to the distal portion of the double-hinged arm.

[0177] Appearance 20. The system according to embodiment 18, wherein when moving from a contracted state to an extended state, (i) the proximal portion of the double-hinged arm opens away from the hub, and (ii) the distal portion of the double-hinged arm opens away from the proximal portion of the double-hinged arm.

[0178] Appearance 21. The system according to embodiment 6, wherein the carrier includes an expandable band arranged around a mechanical actuator.

[0179] Appearance 22. The system according to embodiment 6, wherein the array of microneedles is mechanically connected to a mechanical actuator.

[0180] Appearance 23. The system according to embodiment 22, wherein the array of microneedles is integrally formed with the material of the mechanical actuator.

[0181] Appearance 24. The array of microneedles is Aspect ratio between 2 and 3, Pitch of 1.5 mm or more and 2 mm or less, The system according to embodiment 6, having properties including a sharpness of less than 1 micron.

[0182] Appearance 25. A method for treating a subject with a drug or biotherapy agent, comprising administering the device described in Embodiment 1 to the subject, wherein the device includes a drug or biotherapy payload.

[0183] Appearance 26. A method for treating a subject with a drug or biotherapy agent, comprising administering the system described in aspect 6 to the subject, wherein the system includes a drug or biotherapy agent payload.

[0184] Appearance 27. An assembly is formed by connecting an array of microneedles to a mechanical actuator that can be extended outward from the central longitudinal axis. A method for fabricating an assembly, comprising: placing the assembly within a capsule having a first state in which the capsule restricts the expansion of a mechanical actuator, and then placing the assembly within a second state in which the capsule is reconfigurable at a target site in the object, allowing the constraint by the capsule to be released and the mechanical actuator to expand in order to drive the array of microneedles to engage with tissue at the target site.

[0185] Appearance 28. The method according to embodiment 27, further comprising forming an array of microneedles before connecting to a mechanical actuator.

[0186] Appearance 29. The method according to embodiment 27, wherein connecting the array of microneedles to a mechanical actuator includes integrally forming the array of microneedles with the material of the mechanical actuator.

[0187] Appearance 30. The method according to embodiment 27, wherein connecting the array of microneedles to a mechanical actuator includes positioning the mechanical actuator within an expandable band that supports the microneedles.

[0188] Appearance 31. Aspect ratio between 2 and 3 Pitch of 1.5 mm or more and 2 mm or less, The method according to embodiment 27, further comprising forming an array of characteristic microneedles having a sharpness of less than 1 micron.

[0189] In some embodiments, the apparatus, system, or method provided relates to one or more of the following embodiments, or to some combination of elements thereof. In some embodiments, the apparatus or system described in one or more of these embodiments can be used to carry out the method described in one of the other embodiments. Furthermore, features described with respect to the apparatus or system may be implemented with respect to the method, and vice versa.

[0190] Example 1. It is a system, It is a capsule, The inner surface that defines the internal volume of the capsule, and the digestive tract A capsule comprising a shell having an outer surface sized to pass through a lumen defined by an inner layer, The carrier is sized to fit within the internal volume of the capsule and supports the array of microneedles, allowing the microneedles to penetrate the inner lining of the digestive tract. A mechanical actuator capable of moving outward is provided, and the mechanical actuator is A foldable biasing member comprising a first end and a second end, wherein the first end and the second end include a flexible elastic material having flexibility that allows them to fold toward each other in order to move from an extended state to a contracted state in which a mechanical actuator fits into the internal volume of a capsule, the flexible elastic material further having elasticity that biases the first end and the second end toward each other, moving from the contracted state to the extended state, and moving the carrier outward as the mechanical actuator overcomes or avoids constraints provided by the capsule, A system comprising a holder, which is hinged to the first end of a biasing member and includes a support surface for supporting a carrier that supports an array of microneedles.

[0191] Example 2. The system according to Embodiment 1, further comprising a link mechanism connected to the first end of the folding biasing member.

[0192] Example 3. The linkage mechanism is the system according to Example 2, which includes channels that allow the holder to receive the tips of the microneedle array in a contracted state from the inner surface of the capsule, spaced apart.

[0193] Example 4. The system according to Embodiment 2, wherein the holder is hinged to the first end of the biasing member via a hinge that is at least partially included in the link mechanism.

[0194] Example 5. The system according to Embodiment 4, further comprising a hinge stopper surface, which is included on a holder or link mechanism and is positioned to prevent the hinge from rotating beyond a predetermined limit.

[0195] Example 6. The foldable biasing member is the system described in Example 1, which includes a nitinol wire.

[0196] Example 7. The system according to Embodiment 1, wherein the foldable biasing member is a first foldable biasing member, and the holder is hinged to the sides facing the first foldable biasing member and the second foldable biasing member.

[0197] Example 8. The foldable biasing member and holder are The first holder and the second holder, The first link mechanism, the second link mechanism, the third link mechanism, and the fourth link mechanism, An assembly comprising a first foldable biasing member and a second foldable biasing member, which are arranged within the assembly, and as a result, The first foldable biasing member has opposing ends that are received by the first link mechanism and the second link mechanism, respectively. The second foldable biasing member has opposing ends that are received by the third link mechanism and the fourth link mechanism, respectively. The first holder is hinged to the first link mechanism and the third link mechanism on the side facing them. The system according to Embodiment 1, wherein the second holder is hinged to the second link mechanism and the fourth link mechanism on the side facing them.

[0198] Example 9. The system according to Embodiment 1, wherein the holder is a first holder, which is arranged to be attached to a second holder in a retracted state and has a removable mounting surface configured to release so as to allow the first holder and the second holder to be positioned symmetrically with respect to each other.

[0199] Example 10. The system according to Embodiment 1, comprising at least three holders interconnected by at least three foldable biasing members arranged to extend between laterally adjacent holders.

[0200] Example 11. It is a system, It is a capsule, The first shell part, The second shell section, A joint that detachably attaches the first shell part to the second shell part, An inner surface that defines the internal volume of the capsule, at least partially defined by the first and second shell portions, and a lumen that is at least partially defined by the first and second shell portions and defined by the inner layer of the digestive tract, sized to pass through. A capsule comprising a shell having an outer surface, Sized to fit within the internal volume of the capsule, it is a carrier that supports the array of microneedles and is operable when overcoming or circumventing the constraints provided by the articulation. A system comprising a launcher that is operable to drive a first shell portion and a second shell portion away from a carrier to expose an array of microneedles.

[0201] Example 11A. The system according to Example 11, wherein the launcher is operable to expose the array of microneedles to a position for achieving penetrating engagement with the inner lining of the digestive tract caused by peristaltic contractions of the digestive tract around the array of microneedles.

[0202] Example 12. The system according to Embodiment 11, wherein the launcher portion is mounted within the first shell portion and the second shell portion, respectively, so as to be held therein after the first shell portion and the second shell portion have been driven away from the carrier.

[0203] Example 13. The system according to Embodiment 11, wherein the launcher comprises a coil spring positioned to press against the leverage surface of a core connected to a carrier.

[0204] Example 14. The system according to Example 11, wherein the first and second shell portions include grooves formed to restrict the movement of the core within the capsule, receiving flanges extending from a core connected to a carrier.

[0205] Example 15. The system according to Example 11, wherein the carrier is attached to the core by a releaseable bond in response to a release force smaller than a release force sufficient to disengage the array of microneedles from penetrating engagement with the inner lining of the digestive tract.

[0206] Example 16. A system comprising a mechanical actuator configured for microneedle delivery, wherein the mechanical actuator is a foldable biasing member including a first end and a second end, A folding biasing member comprising a flexible elastic material having flexibility that allows a first end and a second end to fold toward each other in order to move from an expanded state to a contracted state in which they fit into a volume sized to fit into a capsule into which a mechanical actuator can take in, wherein the flexible elastic material further has elasticity that biases the first end and the second end toward each other in order to move from a contracted state to an expanded state, A system comprising a holder including a support surface that is hinged to a first end of a biasing member and configured to support a carrier supporting an array of microneedles, wherein the support surface is configured to support the carrier for outward movement to deploy the microneedles in response to movement from a contracted state to an expanded state.

[0207] Example 17. The system described in Example 16, further comprising a carrier to support the array of microneedles.

[0208] Example 18. The system according to Example 16, further comprising capsules.

[0209] Example 19. The foldable biasing member and holder are The first holder and the second holder, The first link mechanism, the second link mechanism, the third link mechanism, and the fourth link mechanism, An assembly comprising a first foldable biasing member and a second foldable biasing member, which are arranged within the assembly, and as a result, The first foldable biasing member has opposing ends that are received by the first link mechanism and the second link mechanism, respectively. The second foldable biasing member has opposing ends that are received by the third link mechanism and the fourth link mechanism, respectively. The first holder is hinged to the first link mechanism and the third link mechanism on the side facing them. The system according to Embodiment 16, wherein the second holder is hinged to the second link mechanism and the fourth link mechanism on the side facing them.

[0210] Example 20. A device comprising a capsule containing an array of microneedles and a launcher, the device being in an ingestionable form for delivery to the duodenum of a subject, wherein, in response to stimulation or circumstances within or along the duodenum, the launcher releases a first shell portion and a second shell portion of the capsule from each other, and drives the released first shell portion and the second shell portion away from each other, exposing the array of microneedles to a position for achieving penetrating engagement with the inner lining of the duodenum caused by peristaltic contraction of the inner lining of the duodenum around the exposed array of microneedles, thereby facilitating delivery of the payload via the microneedles.

[0211] References to examples or implementations in this specification mean that certain features, structures, operations, or other characteristics described in relation to an example may be included in at least one implementation of this disclosure. This disclosure is not limited to any specific example or implementation described in this specification. The phrases "in one example," "in a particular example," "in one implementation," or "in a particular implementation," or their variations in various parts of this specification, do not necessarily refer to the same example or implementation. Any particular feature, structure, operation, or other characteristic described herein in relation to one example or implementation may be combined with other features, structures, operations, or other characteristics described in relation to any other example or implementation.

[0212] The use of the term "or" in this specification is intended to encompass an inclusive and exclusive OR condition. In other words, A or B or C, where appropriate for the particular use, includes any or all of the following alternative combinations: A alone, B alone, C alone, A and B only, A and C only, B and C only, and any or all of A, B, and C.

Claims

1. It is a system, It is a capsule, The inner surface that defines the internal volume of the capsule, A capsule comprising a shell having an outer surface sized to pass through a lumen defined by the inner lining of the digestive tract, A carrier sized to fit within the internal volume of the capsule and supporting the array of microneedles, A mechanical actuator capable of moving the carrier outward in order to allow the microneedle to penetrate the inner layer of the digestive tract, A foldable biasing member comprising a first end and a second end, wherein the first end and the second end include a flexible elastic material having flexibility that allows them to fold toward each other in order to move from an extended state to a contracted state in which the mechanical actuator fits into the internal volume of the capsule, and the flexible elastic material further has elasticity that biases the first end and the second end toward each other, moving from the contracted state to the extended state, and moving the carrier outward as the mechanical actuator overcomes or avoids constraints provided by the capsule, A system comprising a mechanical actuator, a holder, and a holder, which is hinged to the first end of the biasing member and includes a support surface for supporting the carrier that supports the array of microneedles.

2. The system according to claim 1, further comprising a link mechanism connected to the first end of the folding biasing member.

3. The system according to claim 2, wherein the link mechanism includes channels in which the holder receives the tips of the array of microneedles in the contracted state so as to be spaced apart from the inner surface of the capsule.

4. The system according to claim 2, wherein the holder is hinged to the first end of the biasing member via a hinge that is at least partially included in the link mechanism.

5. The system according to claim 4, further comprising a hinge stopper surface included on the holder or the link mechanism and positioned to prevent the hinge from rotating beyond a predetermined limit.

6. The system according to claim 1, wherein the foldable biasing member includes a nitinol wire.

7. The system according to claim 1, wherein the folding biasing member is a first folding biasing member, and the holder is hinged to the side facing the first folding biasing member and the second folding biasing member.

8. The foldable biasing member and the holder are, The first holder and the second holder, The first link mechanism, the second link mechanism, the third link mechanism, and the fourth link mechanism, An assembly comprising a first foldable biasing member and a second first foldable biasing member, as a result, The first foldable biasing member has opposing ends that are received by the first link mechanism and the second link mechanism, respectively. The second foldable biasing member has opposing ends that are received by the third link mechanism and the fourth link mechanism, respectively. The first holder is hinged to the first link mechanism and the third link mechanism on the side facing them. The system according to claim 1, wherein the second holder is hinged to the second link mechanism and the fourth link mechanism on the side facing them.

9. The system according to claim 1, wherein the holder is a first holder, which is arranged to be attached to the second holder in the retracted state and has a removable mounting surface configured to be released so as to allow the first holder and the second holder to be positioned symmetrically with respect to each other.

10. The system according to claim 1, comprising at least three holders interconnected by at least three foldable biasing members arranged to extend between laterally adjacent holders.

11. It is a system, It is a capsule, The first shell part, The second shell section, The first shell portion is detachably attached to the second shell portion by a joint portion, The inner surface, at least partially defined by the first shell portion and the second shell portion, defines the internal volume of the capsule, A capsule comprising a shell having an outer surface at least partially defined by the first shell portion and the second shell portion, and sized to pass through a lumen defined by the inner layer of the digestive tract, A carrier sized to fit within the internal volume of the capsule and supporting the array of microneedles, A system comprising: a launcher that is operable in overcoming or circumventing the constraints provided by the joint, and which is operable in driving the first shell portion and the second shell portion away from the carrier to expose the array of microneedles.

12. The system according to claim 11, wherein the launcher is operable to expose the array of microneedles to a position for achieving penetrating engagement with the inner lining of the digestive tract caused by peristaltic contraction of the digestive tract around the array of microneedles.

13. The system according to claim 11, wherein the launcher portion is mounted within the first shell portion and the second shell portion, respectively, so as to be held therein after the first shell portion and the second shell portion have been driven away from the carrier.

14. The system according to claim 11, wherein the launcher comprises a coil spring positioned to press against the leverage surface of a core connected to the carrier.

15. The system according to claim 11, wherein the first shell portion and the second shell portion include grooves formed to restrict the movement of the core within the capsule, receiving flanges extending from a core connected to the carrier.

16. The system according to claim 11, wherein the carrier is attached to the core by a releaseable coupling in response to a release force smaller than a release force sufficient to disengage the array of microneedles from penetrating engagement with the inner layer of the digestive tract.

17. A system comprising a mechanical actuator configured for microneedle delivery, wherein the mechanical actuator is A foldable biasing member comprising a first end and a second end, wherein the first end and the second end are made of a flexible elastic material that allows them to fold toward each other in order to move from an extended state to a contracted state that fits into a volume sized to fit into a capsule into which the mechanical actuator can take in, and the flexible elastic material further has elasticity that biases the first end and the second end toward each other, causing them to move from the contracted state to the extended state, A system comprising: a holder, which is hinged to the first end of the biasing member and includes a support surface configured to support a carrier supporting an array of microneedles, wherein the support surface is configured to support the carrier for outward movement to deploy the microneedles in response to movement from the contracted state to the expanded state.

18. The system according to claim 17, further comprising the carrier supporting the array of microneedles.

19. The system according to claim 17, further comprising the aforementioned capsule.

20. The foldable biasing member and the holder are, The first holder and the second holder, The first link mechanism, the second link mechanism, the third link mechanism, and the fourth link mechanism, An assembly comprising a first foldable biasing member and a second first foldable biasing member, as a result, The first foldable biasing member has opposing ends that are received by the first link mechanism and the second link mechanism, respectively. The second foldable biasing member has opposing ends that are received by the third link mechanism and the fourth link mechanism, respectively. The first holder is hinged to the first link mechanism and the third link mechanism on the side facing them. The system according to claim 17, wherein the second holder is hinged to the second link mechanism and the fourth link mechanism on the side facing them.

21. A device comprising a capsule containing an array of microneedles and a launcher, the device being in an ingestionable form for delivery to the duodenum of a subject, wherein, in response to stimulation or circumstances within or along the duodenum, the device releases a first shell portion and a second shell portion of the capsule from each other, the launcher drives the released first shell portion and the second shell portion away from each other, exposing the array of microneedles to a position for achieving penetrating engagement with the inner lining of the duodenum caused by peristaltic contraction of the inner lining of the duodenum around the exposed array of microneedles, the penetrating engagement thereby facilitating delivery of a payload via the microneedles.

22. A device comprising a capsule containing an array of microneedles and a mechanical actuator, wherein the device is in an ingestionable form for delivery to the duodenum of a subject, and in response to stimulation or conditions within or along the duodenum, the device releases the mechanical actuator from the constraint of the capsule, and when the mechanical actuator is released from the constraint of the capsule, it expands outward in a direction away from the central longitudinal axis of the mechanical actuator, driving the array of microneedles into penetrating engagement with the inner layer of the duodenum, the penetrating engagement thereby facilitating delivery of a payload via the microneedles.

23. The mechanical actuator is A foldable biasing member comprising a first end and a second end, wherein the first end and the second end exhibit flexibility that allows them to fold toward each other in order to move from an expanded state to a contracted state, and the biasing member exhibits elasticity that pushes the first end and the second end apart from each other in order to move from the contracted state to the expanded state, The apparatus according to claim 22, comprising: a holder, which is hinged to the first end of the biasing member and includes a support surface for supporting the array of microneedles.

24. The apparatus according to claim 22, wherein the apparatus is entirely formed from one or more biodegradable materials, and is so completely biodegradable that no portion remains that needs to pass through the excrement removed from the object.

25. The apparatus according to claim 22, wherein the mechanical actuator is formed from a structure that allows it to pass through in order to avoid complete obstruction of the lumen of the duodenum by the mechanical actuator when the mechanical actuator is in an outwardly expanded state.

26. The mechanical actuator is A collapsible tube that is compressible toward the central longitudinal axis of the mechanical actuator and expandable away from it, An upper crossbeam and a lower crossbeam joined by lateral columns having a central hinge, A coil having multiple overlapping rotational sections that is wound more tightly in the contracted state than in the expanded state, Multiple curved arms, each attached to a central core at its proximal end and movable so as to move from a contracted state to an expanded state by rotating spirally away from the core at its distal end, The apparatus according to claim 22, comprising a hub connected to a plurality of double-hinged arms, each double-hinged arm including (i) a first hinge connecting the proximal portion of the arm to the hub, and (ii) a second hinge connecting the proximal portion of the arm to the distal portion of the arm.

27. The apparatus according to claim 22, wherein the array of microneedles is arranged around the mechanical actuator and supported by an expandable band configured to expand in response to the expansion of the mechanical actuator.

28. It is a system, It is a capsule, The inner surface that defines the internal volume of the capsule, A capsule comprising a shell having an outer surface sized to pass through a lumen defined by the inner lining of the digestive tract, A carrier sized to fit within the internal volume of the capsule and supporting the array of microneedles, A system comprising a mechanical actuator that is operable to move the carrier outward so that the microneedle penetrates the inner layer of the digestive tract, and includes a flexible elastic material having flexibility that allows the mechanical actuator to contract toward a contracted state, away from an expanded state, toward a contracted state, toward a state in which it fits within the internal volume of the capsule, wherein the flexible elastic material biases the mechanical actuator toward an outward expansion toward the expanded state, and has elasticity that moves the carrier outward as the mechanical actuator overcomes or avoids constraints provided by the capsule.

29. The mechanical actuator comprises a biasing member having a first end and a second end that are foldable toward each other, The system according to claim 28, comprising: a holder, which is hinged to the first end of the biasing member and includes a support surface for supporting the array of microneedles.

30. The system according to claim 28, wherein the capsule is configured to free the mechanical actuator from the constraints of the portion of the digestive tract corresponding to the duodenum.

31. The system according to claim 30, wherein the capsule is configured to decompose in the duodenum to free the mechanical actuator from constraints.

32. The system according to claim 28, wherein the mechanical actuator and the carrier are each configured to move outward in a direction away from the central longitudinal axis of the mechanical actuator.

33. The system according to claim 28, wherein the mechanical actuator comprises a collapsible tube that is compressible toward the central longitudinal axis of the mechanical actuator and expandable away from there.

34. The system according to claim 33, wherein the collapsible tube is formed from a network of interconnected flexible members, the spacing between the members being greater in the expanded state than in the contracted state.

35. The system according to claim 28, wherein the mechanical actuator includes an upper crossbeam and a lower crossbeam joined by a lateral column having a central hinge.

36. The system according to claim 35, wherein at least one of the intermediate hinges moves from below one end of the upper crossbeam to below the opposite end when shifting between the retracted state and the extended state.

37. The system according to claim 35, wherein the central hinges pass each other when shifting between the contracted state and the extended state.

38. The system according to claim 35, wherein the lateral columns include at least one pair of columns, each of which moves between the contracted state and the expanded state, thereby defining a slot.

39. The system according to claim 28, wherein the mechanical actuator includes a coil having a plurality of overlapping rotating parts that are wound more tightly in the contracted state than in the expanded state.

40. The system according to claim 28, wherein the mechanical actuator includes a plurality of curved arms, the proximal ends of which are attached to a central core and the distal ends of which are movable to rotate helically away from the core to move from the contracted state to the extended state.

41. The system according to claim 28, wherein the mechanical actuator is a hub connected to a plurality of double-hinged arms, each double-hinged arm comprising a hub including (i) a first hinge connecting the proximal portion of the double-hinged arm to the hub, and (ii) a second hinge connecting the proximal portion of the double-hinged arm to the distal portion of the double-hinged arm.

42. The system according to claim 41, wherein, in the retracted state, the proximal portion of the double-hinge arm is positioned outward with respect to the central longitudinal axis of the mechanical actuator, relative to the distal portion of the double-hinge arm.

43. The system according to claim 41, wherein when moving from the contracted state to the extended state, (i) the proximal portion of the double-hinged arm opens away from the hub, and (ii) the distal portion of the double-hinged arm opens away from the proximal portion of the double-hinged arm.

44. The system according to claim 28, wherein the carrier comprises an expandable band arranged around the mechanical actuator.

45. The system according to claim 28, wherein the array of microneedles is mechanically connected to the mechanical actuator.

46. The system according to claim 45, wherein the array of microneedles is integrally formed with the material of the mechanical actuator.

47. The array of microneedles is Aspect ratios of 2 to 3, A pitch of 1.5 mm or more and 2 mm or less, The system according to claim 28, comprising the properties including a sharpness of less than 1 micron.

48. A method for treating a subject with a drug or biotherapy agent, comprising administering the device described in claim 22 to the subject, wherein the device includes a drug or biotherapy agent payload.

49. A method for treating a subject with a drug or biotherapy agent, comprising administering the system described in claim 28 to the subject, wherein the system comprises a drug or biotherapy payload.

50. An assembly is formed by connecting an array of microneedles to a mechanical actuator that can extend outward from the central longitudinal axis. A method for manufacturing the assembly, comprising: placing the assembly within a capsule having a first state in which the capsule restricts the expansion of the mechanical actuator, and then placing the assembly within a second state in which the capsule is reconfigurable at a target location in the object, such that the restriction by the capsule is released and the mechanical actuator expands to drive the array of microneedles to engage with tissue at the target location.

51. The method according to claim 50, further comprising forming the array of microneedles before connecting it to the mechanical actuator.

52. The method according to claim 50, wherein connecting the array of microneedles to the mechanical actuator includes integrally forming the array of microneedles with the material of the mechanical actuator.

53. The method according to claim 50, wherein connecting the array of microneedles to the mechanical actuator includes positioning the mechanical actuator within an expandable band that supports the microneedles.

54. Aspect ratios of 2 to 3, A pitch of 1.5 mm or more and 2 mm or less, or The method according to claim 50, further comprising forming the array of microneedles having properties including a sharpness of less than 1 micron.

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