Tablet with needle delivery system having outwardly expanding mechanical actuation

Abstract

to facilitate delivery of biotherapeutics or other payloads. [Solution] A 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 location within a subject, and the mechanical actuator is capable of releasing from capsule constraint in response to a stimulus or condition within or en route to the duodenum or other target location. Upon release from capsule constraint, the mechanical actuator may expand outwardly away from a central longitudinal axis of the mechanical actuator (e.g., in response to a bias provided by a flexible, elastic material of the mechanical actuator), driving the array of microneedles into penetrating engagement with the lining of the duodenum or other target location. Penetrating engagement may facilitate delivery of a biotherapeutic or other payload through 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 July 30, 2020, the entire contents of which are incorporated herein by reference.

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

[0003] Various compounds, such as biotherapeutics (e.g., peptides, proteins, antibodies, and nucleic acids), have traditionally been ineffective for oral delivery because their size is at least 100 times larger than the recognized size limit for orally deliverable drugs. For example, while biotherapeutics can be approximately 150 kilodaltons (kDa), orally deliverable drugs can be approximately 0.5 kDa in size. While biotherapeutics offer superior efficacy and specificity compared to traditional small molecule therapeutics that can be orally delivered and absorbed during the digestive process, they often present challenges in drug delivery. Essentially, the large size of these biotherapeutics traditionally requires frequent delivery via needle injection, such as with a handheld syringe or an intravenous catheter, commonly referred to as an IV. However, injection or infusion can present challenges with patient compliance, high administration costs by trained medical staff, contamination from the injection needle, needle phobia, and an increased risk of systemic infection. Summary of the Invention

[0004] Various embodiments of the present disclosure are directed to tablets or capsules containing compact needle delivery systems that utilize outwardly expanding mechanical actuation to engage and drive needles into the lining of the digestive tract or other body lumen, for example, to facilitate delivery of a therapeutic agent or other payload through such engagement within the body of a subject.

[0005] In one embodiment, a system includes a capsule. The capsule includes a shell having an inner surface defining an interior volume of the capsule. The shell also has an outer surface sized to pass through a lumen defined by the lining of the gastrointestinal tract. The system may also include a carrier sized to fit within the interior volume of the capsule and supporting the array of microneedles. The system further includes a mechanical actuator operable to move the carrier outward to cause the microneedles to penetrate the lining of the gastrointestinal tract. The mechanical actuator includes a foldable biasing member having a first end and a second end. The foldable biasing member includes a flexible, elastic material, the first end and the second end of which are foldable toward each other and having flexibility such that the foldable biasing member can move from an expanded state toward a contracted state in which the mechanical actuator fits within the interior volume of the capsule. The flexible, elastic material urges the first end and the second end away from each other to move from the contracted state toward the expanded state, and may further have elasticity such that the foldable biasing member moves the carrier outward when the mechanical actuator overcomes or circumvents a constraint provided by the capsule. The mechanical actuator may also include a holder hingedly attached to the first end of the biasing member, and the holder may include a support surface for supporting a carrier that carries the array of microneedles.

[0006] In another embodiment, a system includes a capsule. The capsule includes a shell having a first shell portion, a second shell portion, and an articulation portion removably attaching the first shell portion to the second shell portion. The capsule also includes an inner surface defined at least in part by the first and second shell portions and defining an interior volume of the capsule. Further, the capsule includes an outer surface defined at least in part by the first and second shell portions and sized to pass through a lumen defined by the lining of the gastrointestinal tract. The system may also include a carrier sized to fit within the interior volume of the capsule and supporting the array of microneedles. Furthermore, the system may include a launcher operable to overcome or circumvent the constraint provided by the articulation portion and operable to drive the first and second shell portions away from the carrier and expose the array of microneedles.

[0007] In a further embodiment, the system includes a mechanical actuator configured for microneedle delivery. The mechanical actuator includes a collapsible biasing member including a first end and a second end. The collapsible biasing member may include a flexible, resilient material having flexibility such that the first and second ends are collapsible toward each other and move from an expanded state to a contracted state in which the mechanical actuator fits within a volume sized to fit within an ingestible capsule. The flexible, resilient material may further have a resilience that biases the first and second ends away from each other to move from the contracted state to the extended state. The mechanical actuator may also include a holder hingedly attached to the first end of the biasing member. The holder may include a support surface configured to support a carrier that carries an array of microneedles. The support surface may be configured to support the carrier for outward movement to deploy the microneedles in response to movement from the contracted state to the extended state.

[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 a subject's duodenum and releases the first and second shell portions of the capsule from one another in response to a stimulus or condition in or along the duodenum. The launcher drives the released first and second shell portions away from one another, exposing the array of microneedles in a position to achieve penetrating engagement with the duodenal lining caused by peristaltic contractions of the duodenal lining around the exposed array of microneedles. Penetrating engagement facilitates delivery of a payload through the microneedles.

[0009] In a further embodiment, the device includes a capsule containing an array of microneedles and a mechanical actuator. The device is in an ingestible form for delivery to a subject's duodenum, and in response to a stimulus or condition in or along the duodenum, releases the mechanical actuator from constraint by the capsule. Upon release from constraint by the capsule, the mechanical actuator expands outwardly in a direction away from a central longitudinal axis of the mechanical actuator, driving the array of microneedles into penetrating engagement with the lining of the duodenum. Penetrating engagement facilitates delivery of a payload through the microneedles.

[0010] In another example, a system includes a capsule. The capsule includes a shell having an inner surface defining an interior volume of the capsule. The shell also has an outer surface sized to pass through a lumen defined by the lining of the gastrointestinal tract. The system also includes a carrier sized to fit within the interior volume of the capsule and supporting an array of microneedles. The system further includes a mechanical actuator operable to move the carrier outward to cause the microneedles to penetrate the lining of the gastrointestinal 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 in which the mechanical actuator fits within the interior volume of the capsule. The flexible, elastic material further has elasticity that biases the mechanical actuator to expand outward from the contracted state toward the expanded state and causes the carrier to move outward when the mechanical actuator overcomes or circumvents a constraint provided by the capsule.

[0011] In a further example, a method of treating a subject with a drug or biotherapeutic can be provided, which can include administering to the subject a device, such as those described above, which can include a drug or biotherapeutic payload.

[0012] In yet another embodiment, a method of fabricating can be provided. The method can include forming an assembly by coupling an array of microneedles with a mechanical actuator extendable outward from a central longitudinal axis. The method can further include placing the assembly within a capsule having a first state in which the mechanical actuator is constrained by the capsule to prevent expansion. The capsule can be reconfigured at a target location within a subject to a second state in which the capsule is released from constraint and the mechanical actuator is extendable to drive the array of microneedles to engage tissue at the target location.

[0013] These exemplary embodiments are mentioned not to limit or define the scope of the present disclosure, but rather to provide examples to aid in understanding thereof. The exemplary embodiments are described in the Detailed Description section, which provides further explanation. Advantages offered by various embodiments may be further understood by examining this specification. [Brief explanation of the drawings]

[0014] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate one or more specific embodiments and, together with the description of the embodiments, serve to explain the principles and implementations of the particular embodiments.

[0015] [Figure 1] FIG. 1 shows an end view of a retracted, primed system for delivery of a therapeutic agent or other payload within the body, according to certain embodiments of the present disclosure.

[0016] [Figure 2] FIG. 2 illustrates an end view of the system of FIG. 1 in an expanded, deployed state, in accordance with certain embodiments of the present disclosure.

[0017] [Figure 3] FIG. 3 illustrates a perspective view of a tubular actuator in a retracted, ready state that may be utilized with the system of FIG. 1, in accordance with certain embodiments of the present disclosure.

[0018] [Figure 4] FIG. 4 illustrates a perspective view of the tubular actuator of FIG. 3 in an expanded, deployed state, in accordance with certain embodiments of the present disclosure.

[0019] [Figure 5] FIG. 5 illustrates an end view of the tubular actuator of FIGS. 3 and 4 in a retracted, primed state, in accordance with certain embodiments of the present disclosure.

[0020] [Figure 6]FIG. 6 illustrates an end view of the tubular actuator of FIGS. 3-5 in an expanded, deployed state, according to certain embodiments of the present disclosure.

[0021] [Figure 7] FIG. 7 illustrates a perspective view of an expanded, deployed state of an actuator with hinged lateral columns that may be used with the system of FIG. 1, according to certain embodiments of the present disclosure.

[0022] [Figure 8] FIG. 8 illustrates an end view of the actuator of FIG. 7 in an expanded, deployed state, in accordance with certain embodiments of the present disclosure.

[0023] [Figure 9] FIG. 9 illustrates an end view of the actuator of FIGS. 7 and 8 in an intermediate state between a contracted state and a deployed state, according to certain embodiments of the present disclosure.

[0024] [Figure 10] FIG. 10 illustrates an end view of the actuator of FIGS. 7-9 in a retracted, primed state, in accordance with certain embodiments of the present disclosure.

[0025] [Figure 11] FIG. 11 illustrates a perspective view of a coiled actuator in a retracted, ready state that may be utilized with the system of FIG. 1, in accordance with certain embodiments of the present disclosure.

[0026] [Figure 12] FIG. 12 illustrates an end view of the coil actuator of FIG. 11 in a retracted, primed state, in accordance with certain embodiments of the present disclosure.

[0027] [Figure 13] FIG. 13 illustrates an end view of the coil actuator of FIGS. 11 and 12 in an expanded, deployed state, in accordance with certain embodiments of the present disclosure.

[0028] [Figure 14A]FIG. 14A illustrates a perspective view of an expanded, deployed state of an actuator with curved arms that may be utilized with the system of FIG. 1, according to certain embodiments of the present disclosure.

[0029] [Figure 14B] FIG. 14B illustrates an end view of the actuator of FIG. 14A in a retracted, ready state, in accordance with certain embodiments of the present disclosure.

[0030] [Figure 15] FIG. 15 illustrates a side view of a retracted, ready state of an actuator with a double hinged arm that may be used with the system of FIG. 1, according to certain embodiments of the present disclosure.

[0031] [Figure 16] FIG. 16 illustrates a side view of the actuator of FIG. 15 in an expanded, deployed state, in accordance with certain embodiments of the present disclosure.

[0032] [Figure 17] FIG. 17 is a side perspective view illustrating an example of a portion of an array of microneedles that may be utilized in the system of FIG. 1 in accordance with certain embodiments of the present disclosure.

[0033] [Figure 18] FIG. 18 is a flowchart illustrating an exemplary fabrication process according to certain embodiments of the present disclosure.

[0034] [Figure 19] FIG. 19 illustrates an example of the movement of the device used relative to the subject, according to certain embodiments of the present disclosure.

[0035] [Figure 20] FIG. 20 illustrates a perspective view of a retracted, ready state of an actuator with a collapsible biasing member that may be utilized with the system of FIG. 1, according to certain embodiments of the present disclosure.

[0036] [Figure 21]FIG. 21 illustrates a perspective view of the actuator of FIG. 20 in an expanded, deployed state, in accordance with certain embodiments of the present disclosure.

[0037] [Figure 22] FIG. 22 illustrates an exploded view of the actuator of FIGS. 20 and 21, in accordance with a specific embodiment of the present disclosure.

[0038] [Figure 23] FIG. 23 illustrates a partial cross-sectional end view of the actuator of FIGS. 20-22, according to certain embodiments of the present disclosure.

[0039] [Figure 24] FIG. 24 illustrates a perspective view of an expanded, deployed state of an actuator with an additional collapsible biasing member, in accordance with certain embodiments of the present disclosure.

[0040] [Figure 25] FIG. 25 illustrates a perspective view of the actuator of FIG. 24 in a retracted, ready state, in accordance with certain embodiments of the present disclosure.

[0041] [Figure 26] FIG. 26 illustrates a perspective view of an expanded, deployed state of an actuator with a holder attached by a central hinge, in accordance with certain embodiments of the present disclosure.

[0042] [Figure 27] FIG. 27 illustrates a perspective view of the actuator of FIG. 26 in a retracted, ready state, in accordance with certain embodiments of the present disclosure.

[0043] [Figure 28] FIG. 28 illustrates an exploded view of an actuator with capsule shell portions that are deployable relative to a core, according to certain embodiments of the present disclosure.

[0044] [Figure 29]FIG. 29 illustrates an assembly view of an actuator with a leverage surface on the exterior of the core, in accordance with certain embodiments of the present disclosure.

[0045] [Figure 30] FIG. 30 illustrates an assembly view of an actuator with a leverage surface on the interior of the core, in accordance with certain embodiments of the present disclosure.

[0046] [Figure 31] FIG. 31 illustrates the actuator of FIG. 28 in an environment in which it is used, according to certain embodiments of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0047] Examples are described herein in the context of tablets or capsules containing a compact needle delivery system. Those skilled in the art will appreciate that the following description is illustrative only and is not intended to be limiting in any way. Reference will now be made in detail to implementations of the examples illustrated in the accompanying drawings. The same reference indicators are used throughout the drawings and the following description to refer to the same or similar elements.

[0048] For purposes of clarity, not all of the conventional features of the embodiments described herein are shown and described. Of course, it should be understood that in developing any such actual implementation, many implementation-specific decisions will need to be made to achieve the developer's specific goals, such as compliance with application- and business-related constraints, and that these specific goals will vary from implementation to implementation and from developer to developer.

[0049] In an illustrative example, a subject may wish to take a biotherapeutic or other compound without syringe injection, intravenous infusion, and the potential for discomfort or other concerns. To this end, a user may use a device according to the present disclosure to provide a dosage. In this example, the device may be provided in the form of a tablet or capsule that the subject can swallow. The interior of the tablet or capsule contains components that can be deployed within the body to effectively provide an internal injection, which may cause much less tissue damage and fewer systemic effects compared to an external injection or infusion. When the tablet or capsule reaches a target portion of the gastrointestinal tract (e.g., the duodenum), the specialized coating on the tablet or capsule dissolves or decomposes sufficiently to shatter and allow a mechanical actuator within the tablet to expand outward. Various options for the outward-expanding mechanical actuator can be employed, including a stent-like tube that expands vertically or radially, a recoiled coil, a set of unfolded curved arms, a set of double-hinged arms that deploy relative to a central hub and then deploy again relative to a component connected to the hub, or a scissor-lift-like arrangement with centrally hinged lateral columns that emerge upright from a compressed state to an expanded state, with sections of the columns hinged toward each other. Multiple arrays of microneedles are arranged around the mechanical actuator and driven to engage surrounding tissue (e.g., tissue of the mucosal lining of the duodenum) by expanding outward. A drug dose can be delivered to the tissue through the engaged microneedles, such as by flowing through the microneedles if hollow, or by direct absorption if the drug is embedded in a dissolvable composition in the microneedles. After delivery of the dose, the device components can biodegrade, avoiding potential complications that might otherwise prevent the remainder of the device from passing out of the body. Thus, a subject may use the device to administer an internal injection that is ultimately less invasive, less laborious, and / or less bothersome to the subject than the alternative of using an external syringe or intravenous infusion.

[0050] Referring now to the drawings (which are provided for purposes of illustrating principles and are therefore not necessarily to scale), FIGS. 1 and 2 show different configurations of a system 100 for delivering a drug or other payload into the body. System 100 may include a device 101 that may be located within a lumen 102 within the body, which may be surrounded or otherwise at least partially bounded by a lumen wall 103 formed of tissue lining the lumen 102, for example. Device 101 may include or be fitted within a capsule 104. Generally, capsule 104 provides a constraint (e.g., as illustrated in FIG. 1 ) that can be overcome, circumvented, or otherwise released (e.g., as illustrated in FIG. 2 ) at a target location within a subject, allowing device 101 to expand outward and engage tissue at the target location for delivery of a drug or other payload. In various embodiments, device 101 may enable payload delivery without significant obstruction of body lumen 102 and / or without substantial shear forces on the mucosal or other lining or lumen wall 103 of body lumen 102. In some embodiments, device 101 may be constructed entirely from biodegradable materials, rendering device 101 completely biodegradable. Device 101 may be biodegradable to allow device 101 to be absorbed by the subject's body after use such that no portion remains that must pass through bodily waste to be removed from the subject, although in some cases at least a portion of the degraded biodegradable material of device 101 may be removed via excretion.

[0051] Capsule 104 (e.g., FIG. 1) can include a shell 106. Shell 106 can include or be supplemented with one or more layers of similar or different composition to effect changes in function, such as affecting when capsule 104 can dissolve or otherwise release device 101 from constraint by the capsule within a subject. Shell 106 can have or define an exterior surface 108 and an interior surface 110.

[0052] The outer surface 108 of the capsule 104 may be sized to pass through a body lumen 102. For example, the body lumen 102 may correspond to a lumen having a lumen wall 103 defined by the lining of the digestive tract. In some examples, the capsule 104 may meet the criteria for classification as a 000 capsule known by those skilled in the art, although other standardized or custom-type capsules 104 may be used. The capsule 104 may be sized to facilitate function within a particular body portion. For example, a 000-type capsule 104 may have an outer surface 108 with a total length of approximately 26.14 mm (millimeters) and a body diameter of 9.55 mm, which may be suitable for operation or use in a portion of the digestive tract corresponding to the duodenum (e.g., based on the human duodenum, which typically ranges from 25 mm when fully open to approximately 0 mm when fully closed or strangulated during peristalsis). In some embodiments, the length of capsule 104 exceeds or is approximately equal to the expected maximum diameter or other cross-sectional dimension of lumen 102 within the body, thereby allowing device 101 to be pre-positioned in a predetermined orientation in which device 101 is suitably aligned for expansion to engage the surrounding tissue of lumen wall 103 (e.g., device 101 comprises a length of capsule 104 and lumen 102 within the body that is expandably aligned along the diameter of device 101 and lumen 102 within the body).

[0053] The inner surface 110 may form a boundary or otherwise define an interior volume 112 of the capsule 104, for example, in which the device 101 and / or respective components may be disposed. The inner surface 110 may be separated from the outer surface 108 by a wall thickness, such that, for example, the dimensions between respective portions of the inner surface 110 may be reduced from the dimensions of the outer surface 108 by twice the wall thickness. As an illustrative example, a 000-type capsule 104 may have a wall thickness of 0.11 mm, such that the interior volume 112 has an overall length of approximately 25.92 mm (millimeters) and an inner body diameter of 9.33 mm.

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

[0055] The microneedles 116 may correspond to any suitable form of tissue-penetrating member capable of delivering a payload to an associated tissue. In some examples, the microneedles 116 include a dissolvable composition containing the payload, such that, for example, the payload can be absorbed into the engaged tissue as the engaged microneedle dissolves. Additionally or alternatively, the microneedles 116 may be hollow or otherwise include a passageway through which the payload can flow for delivery.

[0056] The microneedles 116 may be suitably sized and positioned for their function. For example, the microneedles 116 may be "micro," meaning that they may be small enough to fit within the capsule 104 with other components of the device 101. In an exemplary embodiment, the microneedles 116 may have a length of approximately 1.5 mm, such that providing the microneedles 116 on opposite sides within the capsule 104 may leave a space of approximately 3 mm in diameter for the capsule 104, leaving approximately 6.33 mm of the approximately 9.33 mm internal diameter available for other components within, for example, a 000-type capsule 104.

[0057] The microneedles 116 may be distributed in any suitable manner. In some embodiments, the microneedles 116 are grouped into arrays 114 that are distributed sequentially relative to one another. For example, while FIG. 1 shows 16 arrays 114 evenly distributed around the circumference, any other number of one or more arrays 114 may be utilized, and may be distributed evenly or unevenly. In general, the utilized arrays 114 may include any number of one or more rows and / or one or more columns of microneedles 116 (or any other cluster or arrangement that may be staggered in rows or columns or may not otherwise be clearly defined). For example, while FIG. 1 shows an arrangement of 16 arrays 114, each having three rows and one column visible, another exemplary arrangement may have six arrays 114 each having two rows and 12 columns, or any other suitable combination of number of arrays, rows, and columns may be utilized. Additionally, although a single microneedle 116 may be utilized for the device 101 or within each array 114, the amount of payload that can be delivered may be increased by increasing the number of microneedles 116 included.

[0058] In some examples, the microneedles 116 and / or array 114 may additionally or alternatively include particular geometric shapes or other particular physical characteristics (such as sharpness and / or pitch) that can facilitate puncturing or other engagement with the respective inner layers of the luminal wall 103 of the body lumen 102. Some examples of such characteristics are further described with respect to FIG. 17 herein.

[0059] 1 as a band that is expandable vertically or radially under the influence of the mechanical actuator 120. However, the carrier 118 is not limited to a band form factor. The carrier 118 may correspond to any suitable structure for supporting the microneedles 116.

[0060] Carrier 118 may interact with mechanical actuator 120 in any suitable manner to move microneedles 116 outward. In some embodiments, carrier 118 and mechanical actuator 120 may correspond to separate structures. For example, in FIG. 1 , carrier 118 is shown as separate from and positioned around mechanical actuator 120, such that, for example, mechanical actuator 120 may start out at least partially out of contact with carrier 118, expand outward, and contact carrier 118 to drive carrier 118, along with the microneedles 116 supported by carrier 118, outward. Alternatively, carrier 118 may start out in at least partial contact with mechanical actuator 120. In some embodiments, carrier 118 and mechanical actuator 120 are coupled together to maintain contact regardless of whether mechanical actuator 120 is expanded or contracted. In some embodiments, carrier 118 may be a subcomponent of mechanical actuator 120, or vice versa. For example, the carrier 118 may be integrally formed with or otherwise correspond to a portion of the mechanical actuator 120 .

[0061] Any suitable mechanical actuator 120 may be used to move the carrier 118. To this end, the mechanical actuator 120 is shown in generalized terms as a dashed functional block in FIG. 1 (and omitted from FIG. 2 for clarity). Various embodiments of suitable mechanical actuators 120 are shown and / or described with reference to other figures herein, and any of these mechanical actuators 120 may be utilized in conjunction with the arrangements shown and / or described with respect to FIG. 1, such as substituting the location indicated by the dashed lines depicting the mechanical actuator 120 in FIG. 1. For example, the mechanical actuators 120 of the other figures herein may be provided without the directly attached microneedles 116 shown in those figures so as to be more easily incorporated into the arrangements shown and / or described with reference to FIG. 1, such that, for example, the microneedles 116 are provided on the carrier 118 without a separate set of mechanical actuators 120 incorporated therein.

[0062] In some embodiments, the carrier 118 is a band and may directly move the microneedles 116 outward in a 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 directly expands in the radial or normal direction. For example, the carrier 118 may be a band that effectively constrains the microneedles 116 to move directly radially / normally and / or to translate or neutralize non-radial or non-normal components into movement from the mechanical actuator 120.

[0063] The mechanical actuator 120 may include suitable structure for providing an outward expansion to move the carrier 118. The structure may include or be coupled to a suitable material for providing the 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 such as that shown in FIG. 2 and / or toward a contracted state such as that shown in FIG. 1). The contraction may allow the mechanical actuator 120 to fit within the interior volume 112 of the capsule. The material may further have or exhibit elasticity that biases the mechanical actuator 120 toward an outward expansion (e.g., away from the state shown in FIG. 1 to the state shown in FIG. 2, or otherwise away from the contracted state toward the expanded state). The outward expansion may cause the carrier 118 to move outward as the mechanical actuator 120 overcomes or circumvents the constraint provided by the capsule 104.

[0064] Any suitable technique can be utilized to facilitate mechanical actuator 120 overcoming or circumventing the constraint provided by capsule 104. In some examples, capsule 104 may shatter or disintegrate at a specific target location within the subject, overcoming the constraint. For example, shell 106 of capsule 104 may include a suitable enteric coating composition and / or thickness to enable disintegration at the target location. The elasticity of the material of mechanical actuator 120 may aid in the disintegration of capsule 104. For example, capsule 104 may disintegrate to a specific thickness or strength that can be overcome by the force provided by pre-loaded mechanical actuator 120. In some examples, capsule 104 may contain a component that activates or ejects mechanical actuator 120, which may be in addition to or instead of releasing the constraint by disintegrating capsule 104, for example. Generally, any suitable technique can be utilized to trigger the release or release of the constraint from mechanical actuator 120, including, but not limited to, constructing capsule 104 in part or in whole with a coating or other material that can cause the release in response to a stimulus or condition within or en route to the duodenum or other target location. For example, release may be triggered in response to a chemical (such as pH), electrical, mechanical, or external stimulus (such as ultrasonic energy that may be applied to affect a particular composition). Once released from the constraint provided by capsule 104, mechanical actuator 120 may provide an appropriate velocity and / or force to drive microneedle 116 into engagement with tissue of the lumen wall 103 of body lumen 102 (such as the position shown in FIG. 2) for delivery of a payload.

[0065] Figure 3 is a perspective view illustrating further examples of structures that may be incorporated into system 100. In some embodiments (such as Figure 3), mechanical actuator 120 may include a collapsible tube 130. Collapsible tube 130 may be compressible toward and expandable away from a central longitudinal axis 124 of mechanical actuator 120 (e.g., in a radial or normal direction, which may correspond to a direction perpendicular to the long axis of lumen 102). For example, Figures 3 and 5 illustrate perspective and end views, respectively, of collapsible tube 130 in a ready, contracted state, while Figures 4 and 6 illustrate perspective and end views, respectively, of collapsible tube 130 in an expanded, deployed state.

[0066] Although the microneedles 116 are shown as being supported by a carrier 118 that is separately attached to the collapsible tube 130, other arrangements are possible, including, but not limited to, arrangements in which the microneedles 116 and / or carrier 118 are instead integrally formed, or in which the carrier 118 corresponds to a band or other separate structure as described with respect to Figures 1 and 2.

[0067] As best seen in FIG. 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 lattice 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 of the members 132, and each window 134 may exhibit a smaller cross-sectional opening in the contracted state compared to the expanded state. In some examples, the members 132 and / or windows 134 may be compressed along the periphery of the collapsible tube 130. For example, the members 132 may be compressed into spaces defined by the windows 134. In some examples (e.g., as best seen by comparing FIGS. 5 and 6 ), the tube 130 may be shown to have a smaller circumference when compressed than when expanded, e.g., rather than collapsing in a manner that protrudes portions inward from the circumference of the collapsible tube 130. In some examples, 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, resilient material. For example, the material may provide sufficient flexibility to allow collapsible tube 130 to compress from an expanded state toward a compressed state, and the material may provide sufficient resilience to bias the material away from the compressed state toward the expanded state, for example, to drive microneedles 116 outward for tissue engagement. In some embodiments, member 132 is comprised of a biodegradable material (e.g., degradable within the GI tract or within a specific target portion thereof). In some embodiments, member 132 is constructed of a material suitable for constructing collapsible tube 130 by 3D printing (three-dimensional printing) or other specific fabrication techniques. Some suitable examples of materials for member 132 may include stereophotolithography (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] In use, the collapsible tube 130 provides a central, generally through passageway in the expanded state, and therefore may prevent or avoid complete obstruction of the lumen of the duodenum or other relevant body cavity 102. Additionally, the collapsible tube 130 may provide normal or radial outward movement of the microneedles 116 into the inner layer of the lumen wall 103 of the body lumen 102, in a direction perpendicular to the long axis of the lumen, to reduce or avoid shear forces that may occur if, for example, the mechanical actuator 120 instead imparts several tangentially oriented components in addition to radially or vertically oriented components.

[0070] FIG. 7 is a perspective view illustrating further examples of structures that may be incorporated into system 100. In some embodiments (such as FIG. 7), mechanical actuator 120 may include hinged columns 138 (individually identified by subscripts A, B, and C). The hinging capabilities of columns 138 may allow mechanical actuator 120 to be compressible toward and expandable away from central longitudinal axis 124 of mechanical actuator 120 (e.g., in a radial or normal direction, which may correspond to a direction perpendicular to the long axis of lumen 102). For example, if FIGS. 7 and 8 show perspective and end views, respectively, of hinged column 138 in an expanded, deployed state, FIG. 10 shows a perspective end view of the corresponding ready, contracted state, while FIG. 9 shows an end view of an intermediate state between the contracted and expanded states.

[0071] 7, the column 138 may form part of a body 140 of the mechanical actuator 120. The body 140 may include the column 138 and cross beams 142 (e.g., upper cross beam 142A and lower cross beam 142B).

[0072] Although the microneedles 116 are shown as being supported by a carrier 118 that is integrally formed with the cross beam 142 of the body 140, other arrangements are possible, including, but not limited to, arrangements in which the microneedles 116 and / or carrier 118 are instead integrally and separately attached, 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 body 140 may be, for example, generally rectangular. The body 140 may define corners 144, such as an upper left corner 144A, an upper right corner 144B, a lower left corner 144C, and a lower right corner 144D, as shown in FIG. 7 . The columns 138 may be positioned laterally relative to the body 140 and may therefore alternatively be referred to as lateral columns. The upper and lower cross beams 142A and 142B may be joined by the columns 138, such as at the corners 144 of the body 140.

[0074] Each column 138 may have a respective hinge 146 (individually identified by the suffixes A, B, and C). The hinges 146 may be positioned toward the center of the column 138 and therefore may alternatively be referred to as center hinges. In some embodiments, the hinges 146 may correspond to a portion of the column 138 that has a reduced cross-section compared to other portions of the column 138, although the hinges 146 may correspond to any suitable structure for facilitating bending or flexing of the column 138 about the hinges 146.

[0075] The column 138 and / or other portions of the body 140 may be formed of a suitable material. In some examples, the material is a flexible, resilient material (e.g., sufficiently flexible to be compressible from an expanded state toward a compressed state to drive the microneedles 116 outward for tissue engagement, and further sufficiently resilient to bias the material toward an expanded state away from the compressed state). In some examples, the material is biodegradable (e.g., degradable 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 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., FIG. 10 ) and an expanded state (e.g., FIG. 7 ). In the expanded state (as shown in FIGS. 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 cross beams 142 directly connected to the column 138. For example, the hinges 146A of the left column 138A in the expanded state can be aligned below the upper left corner 144A and above the lower left corner 144C. During movement from the expanded state to the contracted state, the hinges 146 can move out of such alignment, such as by moving toward each other as the hinges 146 flex. In some embodiments, each hinge 146 moves from below or above one end of the upper cross beam 142 to below or above the opposite end when shifting between the contracted state and the expanded state. For example, in contrast to the above-described position of hinge 146A of left column 138A in the extended position (e.g., FIG. 7), left column 138A in the retracted position (e.g., FIG. 10) may be aligned with (e.g., positioned below or above) the respective ends of cross beam 142 that are not directly connected to column 138 (e.g., below upper right corner 144B and above lower right corner 144D).

[0077] The hinges 146 of different columns 138 may pass each other as they shift between contracted and expanded states during operation. For example, as most readily apparent in FIG. 9 , the hinge 146A of the left column 138A moves toward the right (e.g., as illustrated by arrow 148A), and the hinge 146B of the right column 138B passes the hinge 146B of the right column 130B as it moves toward the left instead (e.g., as illustrated by arrow 148B). The movement of the columns 138 may cause, be caused by, or otherwise coincide with the movement of the top and bottom cross beams 142A, 142B toward each other (as illustrated by arrow 148C).

[0078] The various portions of body 140 may be of approximately equal lengths to facilitate stacking and / or collapsing body 140 into a nested arrangement. For example, each of cross beams 142 and the portions of column 138 on either side of hinge 146 may be of approximately equal lengths. As can best be appreciated with reference to FIG. 10 , utilizing approximately equal lengths may facilitate a compact arrangement in which each portion fits within a predetermined length suitable for fitting within capsule 104.

[0079] Tension member 150 may be attached between multiple columns 138. Tension member 150 may be formed from any suitable material for applying a biasing force. A preferred embodiment may include silicone tubing, but any other type of material and / or configuration with suitable properties may be utilized. In some embodiments, tension member 150 is coupled to one or more of hinges 146. Tension member 150 may provide a force to bias mechanical actuator 120 toward the expanded state during use. In the contracted state of device 101, tension member 150 may be more elongated than in the expanded state. For example, the elongated length of tension member 150 between anchor points 152 in the contracted state of device 101 (e.g., FIG. 10 ) may be greater than the length of tension member 150 between the same anchor points once moved to the expanded state of device 101 (e.g., FIG. 8 ). In some embodiments, anchor points 152 may correspond to surfaces that face each other in the expanded configuration and face away from each other in the contracted configuration. Although anchor points 152 in FIG. 8 are shown located at hinges 146, any other suitable locations along columns 138 may be utilized. Tensioning members 150 may at least partially surround one or more of columns 138 during a shift from the expanded state to the contracted state, increasing the amount of preload force available from tensioning members 150 to bias toward the expanded state. Tensioning members 150 may continue to exert some force on columns 138 in the expanded state. Thus, although columns 138 are shown fully upright in the expanded state (e.g., FIG. 8 ), in some embodiments, columns 138 in the expanded state may exhibit some inward bending or flexion as a result of tensioning members 150.

[0080] Any suitable number of columns 138 may be utilized. In some embodiments, different numbers of columns 138 may be disposed on opposing lateral sides. For example, in FIG. 7 , one column 138A is shown on the left side, while a pair of columns 138B and 138C is shown on the right side. A slot 154 may be defined between adjacent columns, such as between the pair of columns 138B and 138C. As illustrated by arrow 156, the slot 154 may be sized to allow movement through the columns 138 from the opposite side during shifting between the contracted and expanded states. Additionally, the slot 154 may be sized to allow the tension member 150 to at least partially pass therethrough. In some embodiments, including two or more single columns 138 on at least one of the lateral sides 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] In use, body 140, in its expanded state (e.g., with minimal obstruction from passages subdivided by tension member 150), provides a central, generally through passageway, and therefore may prevent or avoid complete obstruction of the lumen of the duodenum or other relevant body lumen 102. Furthermore, body 140 may provide a generally linear outward movement of microneedles 116, thereby perpendicularly engaging the inner layer of the lumen wall 103 of body lumen 102, reducing or avoiding shear forces that may occur if mechanical actuator 120 instead imparts several tangentially oriented components in addition to a linear outward component (such as one oriented along a radial or normal direction, which may correspond to a direction perpendicular to the long axis of lumen 102).

[0082] FIG. 11 is a perspective view illustrating further examples of structures that may be incorporated into system 100. In some embodiments (such as FIG. 11 ), mechanical actuator 120 may include a coil 160. Coil 160 is compressible toward and expandable away from a central longitudinal axis 124 of mechanical actuator 120 (e.g., in a radial or normal direction, which may correspond to a direction perpendicular to the long axis of lumen 102). For example, if FIGS. 11 and 12 show a perspective view and an end view, respectively, of coil 160 in a ready, contracted state, FIG. 13 shows an end view of coil 160 in a corresponding expanded, deployed state.

[0083] As can be best seen with respect to Figure 7, the coil 160 may include multiple overlapping turns 162. For example, in Figure 7, a total of three turns 162A, 162B, and 162C are visible in the bottom half of the coil 160, while a total of two turns 162A, 162B are visible in the top half of the coil 160. The coil 160 is not limited to the number of turns 162 shown, but may include any suitable number of turns 162 to provide a suitable predisposition for the coil to unwind and expand outwardly to drive the microneedle 116 into the inner layer of the lumen wall 103 of the body lumen 102.

[0084] Coil 160 may be formed of a suitable material. In some embodiments, the material is flexible and resilient (e.g., sufficiently flexible to be compressible from an expanded state toward a compressed state to drive microneedles 116 outward for tissue engagement, and further resilient enough to bias the material to expand away from the compressed state toward the expanded state, etc.). In some embodiments, the material is biodegradable (e.g., degradable 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 sheets, rice paper or sheets, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers.

[0085] The coil 160 may facilitate reconfiguration between a contracted state (e.g., FIG. 12) and an expanded state (e.g., FIG. 13). For example, the turns 162 of the coil 160 may be wound tighter (and / or more) in the contracted state (e.g., FIG. 12) than in the expanded state (e.g., FIG. 13). Due to the tightness of the winding, the coil 160 may be pre-positioned to unwind upon release from a constraint, driving the microneedles 116 outward.

[0086] Although the microneedles 116 are shown as being supported by a carrier 118 that is separately attached to the coil 160, other arrangements are possible, including, but not limited to, arrangements in which the microneedles 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 microneedles 116 are shown disposed only on the outer surface or outermost turn 162 of the coil 160, in some examples the microneedles 116 may additionally or alternatively be disposed on the inner surface and / or inner turn 162 of the coil 160.

[0087] In use, the coil 160 provides a central, generally through-path in the expanded state, thus preventing or avoiding complete occlusion of the lumen of the duodenum or other relevant body lumen 102. Furthermore, while the coil 160 may provide movement of the microneedles 116 that includes some tangentially oriented components in addition to straight outward components aligned along the radial or normal direction (and thus may impart some shear force), the amount of shear may be mitigated by adjusting the thickness of the coil 160 (e.g., to impart greater stiffness, which may result in a stronger force for engaging tissue of the lumen wall 103 of the body lumen 102). Additionally, the coil 160 may exhibit a smoother overall surface and / or fewer sharp edges than some other alternatives herein, which may further reduce shear force. Additionally, the coil 160 may present a continuous surface, offering more options for attachment of the array 114, compared to other alternatives herein. Additionally, the form factor of coil 160 may facilitate the use of a roll-to-roll fabrication process, which may be faster, more economical, and / or otherwise beneficial compared to fabrication processes for other alternatives herein.

[0088] FIG. 14A is a perspective view illustrating further examples of structures that may be incorporated into system 100. In some embodiments (e.g., FIG. 14A ), mechanical actuator 120 may include curved arms 170 (individually identified by subscripts A, B, C, D, E, and F). Curved arms 170 are compressible toward and extendable away from central longitudinal axis 124 of mechanical actuator 120 (e.g., radially or normally, which may correspond to a direction perpendicular to the long axis of lumen 102). For example, curved arms 170 are shown in FIG. 14A in an expanded, deployed state and can be curved over one another to reach a ready, contracted state (e.g., as shown in FIG. 14B ).

[0089] Although the microneedles 116 are shown as being supported by a carrier 118 that is integrally formed with the curved arms 170, other arrangements are possible, including, but not limited to, arrangements in which the microneedles 116 and / or carrier 118 are instead integrally and separately attached, 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] 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 a central core 176 at the proximal end 172. For example, the proximal end 172 may be positioned in a slit in the core 176. The proximal end 172 may additionally or alternatively be secured to the core 176 by a suitable adhesive or otherwise joined in a pivotable manner.

[0091] The curved arms 170 may define an arc between the proximal end 172 and the distal end 174. The arc may change as the device shifts between a contracted state and an expanded state (e.g., between the states shown in FIGS. 14A and 14B). The curved arms 170 may be movable such that during operation, the distal ends 174 rotate away from the core 176 in a helical direction moving from the contracted state to the expanded state.

[0092] Any suitable number of curved arms 170 may be used. Thus, although six curved arms 170 are illustrated, a greater or lesser number of arms may alternatively be utilized.

[0093] The curved arms 170 and / or core 176 may be formed of any suitable material, and may or may not differ from one another in the materials utilized. In some embodiments, the material is a flexible, elastic material (e.g., sufficiently flexible to be compressible from an expanded state toward a compressed state to drive the microneedles 116 outward for tissue engagement, and further sufficiently elastic to bias the material toward an expanded state away from the compressed state). In some embodiments, the material is biodegradable (e.g., degradable 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 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 or include 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-pressured bending structure that can pre-position the curved arm 170 toward an equilibrium state that is more open than in the absence of such treatment, so that the curved arm 170 can impart a greater driving force.

[0094] In use, the curved arms 170, in their expanded state, provide a set of generally through passageways (e.g., with minimal obstruction from passageways separated by the curved arms 170), and therefore may prevent or avoid complete obstruction of the lumen of the duodenum or other relevant body lumen 102. Furthermore, the curved arms 170 may provide movement of the microneedle 116 that includes some tangentially oriented components in addition to straight outward components aligned along the radial or normal direction (and thus may impart some shear force), although the magnitude of the normal components of the curved arms 170 may be larger than those provided by the coil 160 or other components described herein (e.g., may provide a stronger force to engage tissue lining the lumen wall 103 of the body lumen 102).

[0095] FIG. 15 is a perspective view illustrating further examples of structures that may be incorporated into system 100. In some embodiments (such as FIG. 15), mechanical actuator 120 may include doubly hinged arms 180 (individually identified by subscripts A, B, and C). Doubly hinged arms 180 are compressible toward and extendable away from a central longitudinal axis 124 of mechanical actuator 120 (e.g., in a radial or normal direction corresponding to a direction perpendicular to the long axis of lumen 102). For example, FIG. 15 illustrates a side view of doubly hinged arms 180 in a ready, contracted state, while FIG. 16 illustrates a side view of a corresponding extended, deployed state.

[0096] Although the microneedles 116 are shown as being supported by a carrier 118 that is integrally formed with the double-hinged arms 180, other arrangements are possible, including, but not limited to, arrangements in which the microneedles 116 and / or carrier 118 are instead integrally and separately attached, 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] 16, the double-hinged arms 180 may extend relative to a hub 182. Any suitable number of double-hinged arms 180 may be utilized. Thus, although three double-hinged arms 180 are illustrated, a front-to-back number of arms may alternatively be utilized.

[0098] Each of the arms 180 may have similar features, although for simplicity, various of such features are identified only with respect to arm 180B in Figures 16 and 17. Each doubly hinged arm 180 may include a first hinge 184 and a second hinge 186, which may define respective subportions of the doubly hinged arm 180. For example, the doubly hinged arm may include a proximal portion 188 and a distal portion 190.

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

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

[0101] First hinge 184 and / or second hinge 186 may correspond to a portion of doubly hinged arm 180 that has a reduced cross-section compared to other portions of doubly hinged arm 180, and / or may correspond to any suitable structure for facilitating bending or flexing of doubly hinged arm 180 about first hinge 184 and / or second hinge 186.

[0102] The double-hinged arms 180 and / or other associated components may be formed of a suitable material. In some examples, the material is a flexible, resilient material (e.g., sufficiently flexible to be compressible from an expanded state toward a compressed state to drive the microneedles 116 outward for tissue engagement, and further sufficiently resilient to bias the material toward an expanded state away from the compressed state). In some examples, the material is biodegradable (e.g., degradable 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 sheets, rice paper or sheets, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers.

[0103] The doubly hinged arm 180 may facilitate reconfiguration between a contracted state (e.g., FIG. 15 ) and an expanded state (e.g., FIG. 16 ). In the contracted state (e.g., FIG. 15 ), a proximal portion 188 of the doubly hinged arm 180 may be positioned outwardly of a distal portion 190 of the doubly hinged arm 180 relative to a central longitudinal axis 124 of the mechanical actuator 120 (such that, for example, the distal portion 190 is hidden from view in FIG. 15 ). The proximal portion 188 of the doubly hinged arm 180 may open away from the hub 182 (e.g., as shown by arrows 194) when moving from the contracted state (e.g., FIG. 15 ) to the expanded state (e.g., FIG. 16 ). For example, the proximal portion 188 may pivot about the first hinge 184, such as due to the properties of the materials included therein. Additionally, distal portion 190 of doubly hinged arm 180 may swing away from proximal portion 188 of doubly hinged arm 180 (e.g., as illustrated by arrow 196). For example, distal portion 190 may pivot about second hinge 186, such as due to the properties of the materials involved. In some embodiments, microneedles 116 may be positioned to face toward the interior of device 101 before deployment (e.g., as shown by the solid lines for central doubly hinged arm 180 in FIG. 16 ) and face outward from device 101 after deployment (e.g., as shown by the dashed-dotted lines for central doubly hinged arm 180 in FIG. 16 ). For example, microneedles 116 may shift from an inward-facing position to a position facing outward from the device as a result of deployment about second hinge 186.

[0104] In use, the doubly hinged arms 180, in their expanded state, provide a set of generally through passageways (e.g., with minimal obstruction from passageways separated by the doubly hinged arms 180), and therefore may prevent or avoid complete obstruction of the lumen of the duodenum or other relevant body lumen 102. Furthermore, the doubly hinged arms 180 may provide movement of the microneedle 116 that includes some tangentially oriented components in addition to linear outward components aligned along the radial or normal direction (and thus may impart some shear force), although the magnitude of the normal components of the doubly hinged arms 180 may be larger than those provided by the coil 160 or other components described herein (e.g., may provide a stronger force to engage tissue lining the lumen wall 103 of the body lumen 102).

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

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

[0107] Suitable dimensions of the physical features of the microneedles 116 can be implemented to achieve the desired outcome of microneedle engagement with the target tissue and release of the payload into the tissue. In some examples, the combination of features can mitigate the "bed of nails" effect, in which forces are sufficiently distributed among multiple supports to prevent or reduce the effectiveness of support penetration into a surface. As an example, for a microneedle 116 having a length L of approximately 1.5 mm, an aspect ratio of 2 to 3, inclusive, and / or a pitch of 1.5 to 2 mm, inclusive, can mitigate the "bed of nails" effect when engaging tissue of the duodenum or other relevant lining of the luminal wall 103 of the body lumen 102.

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

[0109] FIG. 18 is a flowchart illustrating an exemplary process 1800 of fabrication, according to some embodiments.

[0110] The process 1800 at 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 FIG. 17 and / or by any other combination of features and fabrication processes. Any suitable fabrication process or technique may be utilized to form the microneedles 116. As non-limiting examples, the process may include 3D printing and / or the use of a set of one or more dies capable of imparting the shape of the microneedles 116 to a suitable material. As a further example, roll-to-roll stamping may be utilized.

[0112] Operation 1810 may include coupling the microneedles 116 to the mechanical actuator 120. In some embodiments, the array 114 of microneedles 116 is formed prior to coupling 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 coupled to the mechanical actuator 120). In some embodiments, the array 114 of microneedles 116 is mechanically coupled by integrally forming the array 114 of microneedles 116 into the material of the mechanical actuator 120. For example, the array 114 may be printed or otherwise fabricated in the same printing or other fabrication process that forms the material of the mechanical actuator 120. In some embodiments, the array 114 is coupled through the use of intervening structures. For example, the mechanical actuator 120 may be disposed within an expandable band or other carrier 118 that supports the microneedle 116 (such as in FIG. 1 ), which may include alternatives for the mechanical actuator 120 to be fixed or not fixed to the expandable band or other carrier 118.

[0113] Operation 1810 may also include forming the mechanical actuator 120. Such fabrication may generate a portion or all of the mechanical actuator 120 in an equilibrium state from which the mechanical actuator 120 may be compressed to reach a contracted state (such as may be provided by capsule 104) in which the mechanical actuator 120 is ready to expand upon release from a constraint. The carrier 118 and / or array may be coupled to the mechanical actuator 120 before and / or after compression from the equilibrium or expanded state.

[0114] Any suitable fabrication process or technique may be utilized to form mechanical actuator 120. In some embodiments, all or at least a portion of mechanical actuator 120 may be produced by 3D printing, SLA, or other additive or subtractive fabrication processes. In some embodiments, the material of 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 prestressed or preloaded structure that aids in the function of mechanical actuator 120. In some embodiments, a roll-to-roll process may be utilized. As an illustrative example, in some embodiments, to produce coil 160, the material may be provided as a sheet or film from a roll-to-roll process, wound around a mandrel, with microneedles on the outermost layer, and cut into portions that can be removed from the mandrel for insertion into a capsule.

[0115] Any suitable material or combination of materials may be utilized to create and / or connect the respective elements during fabrication of the assembly including the mechanical actuator 120 and the microneedles 116. In some embodiments, the material is a flexible, elastic material (e.g., sufficiently flexible to be compressible from an expanded state toward a compressed state to drive the microneedles 116 outward for tissue engagement, and further sufficiently elastic to bias the material toward an expanded state away from the compressed state). In some embodiments, the material is biodegradable (e.g., degradable in the digestive tract) and / or suitable for construction by 3D printing or other specific fabrication techniques. Some examples of suitable materials may include stereophotolithography (SLA) 3D printed durable resin, 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 or include at least one film layer. In some examples, the material may include a cast foam, such as may be produced in a pre-tensioned state, which may impart a certain bias to contribute to the transition from the contracted state to the expanded state.

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

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

[0118] 19 illustrates an example of the movement of device 101 used on subject 1902. For example, device 101 made according to process 1800 and / or otherwise according to other disclosures herein may be used to treat subject 1902. Device 101 may be introduced into the subject's stomach 1906. For example, device 101 may be contained in a tablet or other ingestible form that allows device 101 to be swallowed and passed through the subject's mouth 1910 and esophagus 1912 into the subject's stomach 1906 (e.g., as indicated by arrow 1908). Device 101 may pass from stomach 1906 to duodenum 1914 (e.g., as indicated by arrow 1916). For example, although device 101 is shown in the duodenum 1914 as an example of a suitable target location for actuation of device 101, the target location may alternatively include any other location within the GI tract, such as the distal small intestine (i.e., jejunum and ileum) 1918, the large intestine 1920, or the colon 1922. Device 101 may be actuated at the target location in response to stimuli and / or conditions present within or along the way to the target location. Upon actuation, microneedles 116 (not shown within device 101 in FIG. 19 ) may expand outward into tissue at the target location to deliver a drug or other payload. Suitable payloads may include, for example, small molecules and biotherapeutics (including, for example, 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 (e.g., 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 within other waste products.

[0119] FIG. 20 is a perspective view illustrating further examples of structures that may be incorporated into system 100. In some embodiments (such as FIG. 20 ), mechanical actuator 120 may include a collapsible biasing member 220. The collapsible ability of collapsible biasing member 220 may allow mechanical actuator 120 to be compressible toward and expandable away from a central longitudinal axis 124 of mechanical actuator 120 (e.g., in a radial or normal direction, which may correspond to a direction perpendicular to the long axis of lumen 102). For example, FIG. 20 illustrates a perspective view of collapsible biasing member 220 in a ready, contracted state, while FIG. 21 illustrates a perspective view of the corresponding expanded, deployed state. Additionally, FIG. 22 illustrates an exploded assembly view, and FIG. 23 illustrates a partial cross-sectional end view along the line indicated in FIG. 20 .

[0120] 22, the collapsible biasing member 220 may be associated with a holder 222. For example, the collapsible biasing member 220 may be hingedly attached to the holder 222.

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

[0122] 22 , the collapsible biasing member 220 and / or the holder 222 may be associated with a linkage 224. For example, the collapsible biasing member 220 and the holder 222 may be hingedly attached via the linkage 224. The linkage 224 at one end or portion may, for example, receive or otherwise coupleable or connected to the collapsible biasing member 220 and at another end or portion may be hinged or otherwise coupleable or connected to the holder 222.

[0123] Any suitable hinge 225 may be utilized. For example, as shown in FIG. 22 , hinge 225 includes a post 226 and a corresponding seat 228 positioned to receive and allow rotation of or relative to post 226. While the illustration in FIG. 22 shows seat 228 as a hook formed within holder 222 and post 226 supported by linkage 224, other variations may be suitable. For example, the relative positioning may be reversed, such that post 226 is supported by holder 222 while seat 228 is supported by linkage 224 (e.g., similar to the arrangement in FIG. 24 ). In some embodiments, seat 228 may correspond to a closed collar rather than an open hook. A living hinge or other hinge interface may additionally or alternatively be used to connect holder 222 to linkage 224 and / or collapsible biasing member 220.

[0124] The collapsible biasing member 220, holder 222, linkage 224, hinge 225, and / or other associated components may be formed from suitable materials. In some examples, at least a portion of the material is a flexible, resilient material (e.g., sufficiently flexible to allow compression from an expanded state toward a compressed state to drive the microneedles 116 outward for tissue engagement, and further sufficiently resilient to bias the material to expand away from the compressed state toward the expanded state, etc.). In some examples, the material is biodegradable (e.g., degradable 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 sheets, rice paper or sheets, 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., that may be passed via excretion). In some embodiments, the material of the foldable biasing member 220 may include a metal such as nitinol or a related alloy. In some embodiments, superelastic nitinol may be used, which may exhibit improved performance compared to thermoset nitinol (e.g., which may exhibit memory). For example, superelastic nitinol may be significantly bent and strained without permanent deformation. Nitinol may be capable of collapsing into a compressed state and provide adequate expansion forces to actuate the microneedles 116. Nitinol is also suitably durable in a collapsed state for a significant amount of time, e.g., capable of being held in a stressed state without significant plastic deformation, creep, and / or other degradation that may negatively impact performance. Furthermore, while the foldable biasing member 220 is shown in a multiple wire form factor, any other suitable form factor may be utilized, including, but not limited to, individual wires or bars. In some embodiments, a section of sheet metal may additionally or alternatively be utilized. Stainless steel or other materials suitable for use in springs may additionally or alternatively be utilized.

[0126] Any suitable number of collapsible biasing members 220, holders 222, and / or linkages 224 may be utilized, and the respective numbers may be similar or different relative to one another. For example, while a total of four collapsible biasing members 220, two holders 222, and four linkages 224 are shown in FIG. 21 , one, two, three, four, or any other number may be utilized. While elements with the same name may each have similar features, for simplicity and to avoid obscuring the figure, various such features are primarily identified with reference to only the top left portion of such features in FIG. 21 .

[0127] The collapsible biasing member 220 may include a first end 230 and a second end 232. The flexibility of the collapsible biasing member 220 allows the first end 230 and the second end 232 to fold toward each other, such as moving from an expanded state (e.g., FIG. 21 ) toward a contracted state (e.g., FIG. 20 ). Conversely, the resilience of the collapsible biasing member 220 may bias the first end 230 and the second end 232 away from each other, such as moving from a contracted state (e.g., FIG. 20 ) toward an expanded state (e.g., FIG. 21 ).

[0128] Collapsible biasing member 220 (e.g., at its ends) may be received by or otherwise covered with linkages 224. For example, as shown in FIG. 21 , first end 230 is received within and covered by first linkage 224A, while second end 232 is received within and covered by second linkage 224B. Covering both ends of collapsible biasing member 220 may prevent exposure to sharp edges or other puncture risks during passage through the body. For example, if collapsible biasing member 220 is formed of a non-biodegradable material, linkage 224 may also be formed of a non-biodegradable material as a safety measure during passage through the digestive tract. In some embodiments, a coating of silicone or other material may be disposed around collapsible biasing member 220 (e.g., between first linkage 224A and second linkage 224B) to prevent exposure of collapsible biasing member 220 to metal or other materials.

[0129] As best seen in FIG. 23 , the linkage 224 may define a channel 234. The channel 234 may be sized to receive the holder 222, the microneedle 116, and / or the carrier 118. For example, the channel 234 may have a height, width, and / or depth that allow such components to at least partially fit within. The channel 234 may be sized such that the microneedle 116 is positioned so that it does not contact the capsule 104 when the device 101 is in a compressed state. Maintaining the microneedle 116 out of contact with the capsule 104 may prevent dulling of the microneedle 116, which may otherwise reduce its effectiveness upon deployment.

[0130] The holder 222 may include features suitable for engaging other components. For example, as best seen in FIG. 22, the holder 222 may include a support surface 236 that may support the carrier 118 and / or microneedles 116 during use. While the support surface 236 is positioned to receive a separately attached carrier 118 (e.g., by adhesive, overmolding, or other attachment technique), the support surface 236 may support the carrier 118 in other ways, such as by being integrally formed therewith or by engaging a band or other separate structure as described with respect to FIGS. 1 and 2.

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

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

[0133] Upon release from the constraint, the collapsible biasing member 220 may expand outward, such as by at least partially straightening, to move away from the folded state (e.g., moving from the state shown in FIG. 20 to the state shown in FIG. 21). In response to the outward expansion, linkages 224 that face each other, are adjacent to, or are aligned with each other, may be moved away from each other (e.g., as can be seen in FIG. 21 with first linkage 224A and second linkage 224B displacing away from each other from the starting position shown in FIG. 20).

[0134] Also, in response to the outward expansion, rotation may occur relative to the hinge 225 (e.g., about the post 226 and seat 228). Upon rotation about the hinge 225, the linkage 224A may be reoriented such that the channel 234 moves at least partially away from the carrier 118, exposing the microneedles 116. Also, in response to the outward expansion, the microneedles 116 may be moved outward for engagement with surrounding tissue.

[0135] Additional features may be included to control and / or limit deployment. As one example, which may be most apparent in FIG. 22 , the holder 222 may include a removable attachment surface 238. The removable attachment surface 238 may be on the underside of the holder 222 and / or opposite the support surface 236. For example, the removable attachment surface 238 is shown in FIG. 22 as being disposed on the underside of a protruding stem that extends away from the support surface 236. As best apparent in FIG. 21 , the removable attachment surfaces 238A and 238B of the opposing holders 222A and 222B may face each other in a spaced-apart relationship in the expanded state during use. In contrast, as best apparent in FIG. 20 , in the contracted state, the removable attachment surfaces 238A and 238B of the opposing holders 222A and 222B may contact and / or engage each other. For example, releasable attachment surfaces 238A and 238B may be releasably attached by a releasable degradable adhesive or other feature in response to conditions encountered within lumen 102. Engagement of opposing releasable attachment surfaces 238A and 238B may hold opposing holders 222A and 222B aligned relative to one another and prevent one side (e.g., the left or right side in FIG. 20 ) from expanding before the other during reconfiguration from a contracted state to an expanded state. For example, releasing opposing releasable attachment surfaces 238A and 238B (e.g., in response to conditions within lumen 102) may cause central portions of opposing holders 222A and 222B to move away from one another for deployment, allowing opposing holders 222A and 222B to remain in a symmetrical or parallel orientation during deployment. Such a symmetrical or parallel orientation may facilitate effective engagement by all or a substantial portion of the microneedles 116 on the carrier 118 and may avoid angled deployment that may place only some select microneedles 116 in a position suitable for engagement with surrounding tissue at the end of the holder 222. Additionally or alternatively, the opposing holders 222A and 222B may be held in a parallel orientation prior to deployment by a releasable collar or clamp around the exterior of the assembly in addition to or instead of the releasable mounting surfaces 238 on the interior of the assembly.

[0136] In some embodiments, deployment may be controlled and / or constrained by hinge stops 240. For example, as best seen in FIG. 22 , hinge stops 240 may include hinge stop surfaces 242 on holder 222 and / or hinge stop surfaces 244 on linkage 224. Hinge stop surfaces 242 on holder 222 and / or hinge stop surfaces 244 on linkage 224 may be positioned to contact or block each other and / or other components during relative rotation to deploy. The hinge stops may prevent over-rotation of holder 222 relative to linkage 224 and / or collapsible biasing member 220 beyond a predetermined limit during use. Preventing over-rotation may prevent over-extension, displacement, and / or other misalignment or uneven actuation of deploying microneedles 116. As an illustrative example, the hinge stop 240 may prevent rotation between the holder 222 and the linkage 224 beyond an angle of 80°, although 60°, 65°, 70°, 75°, 80°, 85°, 90°, 95°, 100°, or other maximum angles may also be utilized.

[0137] In use, the collapsible biasing members 220, in their expanded state (e.g., between or around the collapsible biasing members 220), may provide a central generally through passageway and / or bypass passageway, thus preventing or avoiding complete occlusion of the lumen of the duodenum or other relevant body lumen 102. Additionally, the collapsible biasing members 220 may provide a generally linear outward movement of the microneedles 116, thereby perpendicularly engaging the inner layer of the lumen wall 103 of the body lumen 102, reducing or avoiding shear forces that may occur if the mechanical actuator 120 instead imparts several tangentially oriented components in addition to a linear outward component (such as one oriented along a 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 illustrating a further embodiment of a structure that may be incorporated into system 100. Figure 24 illustrates another embodiment in which mechanical actuator 120 may include a collapsible biasing member 220. Various features of Figure 24 may correspond to those described above with respect to Figures 20-23, and for the sake of brevity, a description of such features will not be repeated. Figure 24 illustrates a perspective view of collapsible biasing member 220 in an expanded, deployed state, and Figure 25 illustrates a perspective view of the corresponding ready, contracted state.

[0139] FIG. 24 illustrates an embodiment in which three or more holders 222 are utilized. For example, in FIG. 24, three holders 222 are included. Each holder 222 is illustrated hingedly attached to opposite sides or ends. For example, each holder 222 is shown positioned to engage a respective pair of linkages 224. Three linkages 224 are shown at each end of the device 101 for a total of six linkages 224. In contrast to the arrangement of FIG. 21, which includes two collapsible biasing members 220 both extending from one linkage 224 and both housed within a single other linkage 224, the arrangement of FIG. 24 includes a collapsible biasing member 220 extending from one linkage 224 to multiple other linkages 224. The collapsible biasing member 220 may extend from a single linkage 224 to multiple laterally adjacent linkages 224. For example, on the right side of FIG. 24, one foldable biasing member 220 extends from an upper link mechanism 224 to a laterally adjacent left link mechanism 224 in a counterclockwise direction, while another foldable biasing member 220 extends from the upper link mechanism 224 to a laterally adjacent right link mechanism 224 in a clockwise direction.

[0140] Figure 24 illustrates an embodiment in which hinge 225 is provided in a different form factor than that shown in Figures 20-23. For example, although hinge 225 of Figure 24 includes a post 226 supported by holder 222 and a seat 228 supported by linkage 224, other arrangements may utilize other hinged interface options described herein.

[0141] Figure 24 further illustrates an embodiment in which the hinge stop 240 is provided in a different form factor than that shown in Figures 20-23. For example, the hinge stop 240 of Figure 24 on the holder 222 includes one hinge stop surface 242 formed as a flange or extension that is positioned to engage another hinge stop surface 244 on the linkage 224 during unfolding rotation to prevent or mitigate over-rotation.

[0142] Figure 26 is a perspective view illustrating a further example of a structure that may be incorporated into system 100. Figure 26 illustrates another example in which mechanical actuator 120 may include a collapsible biasing member 220. Various features of Figure 26 may correspond to features described above with respect to Figures 20-23 and / or Figures 24 and 25, and for the sake of brevity, a description of such features will not be repeated. Figure 26 illustrates a perspective view of collapsible biasing member 220 in an expanded, deployed state, and Figure 27 illustrates a perspective view of a corresponding ready, contracted state.

[0143] Figure 26 shows an embodiment in which a hinge 225 is coupled to a central portion of the holder 222. For example, a single hinge 225 may couple the holder 222 to the rest of the device 101, as opposed to the arrangements of Figures 20-23 and / or 24 and 25, where, for example, the holder 222 engages multiple hinges 225 at opposing ends or sides. By coupling the holder 222 via a single hinge, the holder 222 may be provided with the freedom to continue to rotate during deployment, for example, so that when one end engages surrounding tissue, the opposite end can continue to rotate and also engage surrounding tissue.

[0144] 28 is a perspective view illustrating a further example of a structure that may be incorporated into system 100 (e.g., instead of and / or in conjunction with other features herein). Device 101 may include core 250. Core 250 is deployable from capsule 104 during use.

[0145] Although the microneedles 116 are shown as being supported by a carrier 118 that is separately attached to the core 250, other arrangements are possible, including, but not limited to, arrangements in which the microneedles 116 and / or carrier 118 are instead integrally formed.

[0146] The capsule 104 may include features that facilitate the reception 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 may be combined to form the capsule 104 for use. The capsule 104 may include a matching profile or shape to the core 250. For example, the capsule 104 in FIG. 28 is shown with three grooves 256, each sized to receive three flanges 257 defined by the core 250, although other numbers and / or sizing may be utilized. The flanges 257 may, for example, provide a mounting surface for the 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, such as by providing a space in which the microneedle 116 may be positioned without contacting other portions of the capsule 104 in a manner that could otherwise lead to dulling of the microneedle prior to use.

[0147] Device 101 may include launcher 258. While launcher 258 is shown in FIG. 28 as a spring, it may correspond to any structure that separates first shell portion 252 and second shell portion 254 from one another and / or from core 250 during use. Other non-limiting examples may include the use of an expandable material (such as a superabsorbent polymer) and / or a propellant or other gas expansion. Launcher 258 may be attached and / or otherwise retained within first shell portion 252 and / or second shell portion 254, allowing core 250 to be independent or separate from launcher 258. In some embodiments, a portion of launcher 258 may additionally or alternatively be retained within or coupled to core 250 and / or otherwise separate from first shell portion 252 and / or second shell portion 254.

[0148] Launcher 258 may interact with and / or respond to other suitable structures. As one example, core 250 may include at least one leverage surface 260. For example, in FIG. 29, leverage surfaces 260 are located on either end of the exterior of core 250, providing a surface against which launcher 258 can be pressed during use. In FIG. 29, launcher 258 is located completely outside of core 250.

[0149] In some embodiments, the associated structure may be at least partially within core 250. For example, in FIG. 29 , core 250 includes an internal hollow cavity that terminates at leverage face 260. A spring or other structure of launcher 258 may be positioned to extend at least partially within core 250, for example, to press against leverage face 260 during use. In some embodiments, core 250 may be completely hollow, allowing components of launcher 258 to abut, contact, or otherwise engage one another through core 250.

[0150] The first and second shell portions 252, 254 may be removably attached together during use by articulation portion 262 (e.g., FIG. 29 ). Articulation portion 262 may extend, for example, around the circumference of capsule 104. Articulation portion 262 may correspond to a coating or other suitable structure that may degrade or otherwise cause release in response to a stimulus or condition within or along the duodenum or other target location, such as in response to a chemical (e.g., pH), electrical, mechanical, or external stimulus (e.g., ultrasonic energy that may be applied to affect a particular composition). Articulation portion 262 may provide sufficient strength to hold first and second shell portions 252, 254 in engagement with one another, despite the presence of launcher 258, prior to degradation or release.

[0151] The launcher 258 may be operable or activated upon overcoming or avoiding the constraint provided by the articulation portion 262. For example, during use, the capsule 104 may reach the duodenum or other target location and begin to disintegrate and / or release. This induces the launcher 258 to move the first and second shell portions 252 and 254 away from each other and / or drive the core 250 (e.g., shift from the retracted state shown in either FIG. 29 or FIG. 30 to the deployed state shown in FIG. 28). In embodiments in which the launcher 258 includes a spring, the spring may press against the leverage surface 260 to drive the first and second shell portions 252 and 254 apart. In embodiments in which the launcher 258 includes an expandable material, fluid from the target location may enter and cause a chemical reaction, e.g., causing expansion to drive the first and second shell portions 252 and 254 apart.

[0152] The launcher 258, which drives the first and second shell portions 252 and 254 apart, can expose the microneedles 116 in a suitable position for penetrating the surrounding tissue. For example, with reference to FIG. 31 , tissue of the lumen wall 103 of the duodenum or other target location can contract around the core 250, such as in response to peristaltic contractions. Such contraction around the core 250 can provide sufficient force to achieve penetrating engagement of the microneedles 116 with the lining of the duodenum or other target location. Penetrating engagement can result in the microneedles 116 remaining engaged with the tissue without a suitable release force. In various embodiments, the carrier 118 of the microneedles 116 can be attached to the core 250 with an adhesive or other type of bond configured to release when subjected to a release force less than the magnitude of the release force. As a result, the carrier 118 of the microneedles 116 can separate from the core 250 and remain engaged with the tissue as the tissue contracts during peristaltic or other cycles. Maintaining engagement with tissue can, for example, facilitate delivery of a payload via the microneedle 116. The release force can vary depending on the microneedle 116 placement performed, and the release force can be adjusted based on the coupling technology utilized.

[0153] Core 250, launcher 258, and / or other associated components may be formed of suitable materials. In some examples, at least a portion of the material is a flexible, resilient material (e.g., flexible enough to compress launcher 258 to drive first shell portion 252 and second shell portion 254 apart, and further resilient enough to bias the material toward expansion, etc.). In some examples, the material is biodegradable (e.g., degradable 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 sheets, rice paper or sheets, polylactic acid, nylon, polyester, PVA (polyvinyl alcohol), or corn-based polymers. In some examples, the materials used may include non-biodegradable materials (e.g., that can be passed via excretion). By way of non-limiting example, materials may include stainless steel or other metals (such as a coil spring or other spring member for launcher 258), plastics (such as for core 250, first shell portion 252, and / or second shell portion 254), or other substances.

[0154] The foregoing description of some embodiments has been presented for purposes of illustration and description only and is not intended to be exhaustive or to limit the disclosure to the precise form disclosed. Numerous modifications and adaptations will be apparent to those skilled in the art without departing from the spirit and scope of the disclosure. For example, more or fewer steps than the processes described herein may be performed in accordance with the present disclosure. Additionally, other structures may perform one or more steps of the processes described herein.

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

[0156] Aspect 1. A device comprising a capsule containing an array of microneedles and a mechanical actuator, the device in an ingestible form for delivery to the duodenum of a subject, wherein in response to a stimulus or condition within or during the duodenum, the mechanical actuator releases from constraint by the capsule, and upon release from constraint by the capsule, the mechanical actuator expands outward in a direction away from a central longitudinal axis of the mechanical actuator, driving the array of microneedles into penetrating engagement with the lining of the duodenum, the penetrating engagement facilitating delivery of a payload through the microneedles.

[0157] Aspect 1A. The mechanical actuator is a collapsible biasing member including a first end and a second end, the biasing member exhibiting flexibility that allows the first end and the second end to fold toward each other for movement from the expanded state toward the contracted state and exhibiting resilience that biases the first end and the second end away from each other for movement from the contracted state toward the expanded state; 2. The device of embodiment 1, comprising: a holder hingedly attached to the first end of the biasing member and including a support surface for supporting the array of microneedles.

[0158] Aspect 2. The device of embodiment 1, wherein the device is formed entirely from one or more biodegradable materials, whereby the device is fully biodegradable such that no portions remain that require passage through bodily waste to be removed from the subject.

[0159] Aspect 3. The device of embodiment 1, wherein the mechanical actuator is formed from a structure that allows passage of the mechanical actuator in an outwardly expanded state of the mechanical actuator to avoid complete obstruction of the lumen of the duodenum by the mechanical actuator.

[0160] Aspect 4. The mechanical actuator is a collapsible tube compressible toward and expandable away from a central longitudinal axis of the mechanical actuator; upper and lower cross beams joined by lateral columns having central hinges; a coil having multiple overlapping turns that are wound more tightly in the contracted state than in the expanded state; a plurality of curved arms attached at their proximal ends to a central core and movable at their distal ends to rotate helically away from the core to move from a contracted state to an expanded state; and a hub coupled to a plurality of double-hinged arms, each of the double-hinged arms including: (i) a proximal portion of the arm attached to the hub; and (ii) a second hinge connecting a proximal portion of the arm to a distal portion of the arm.

[0161] Aspect 5. 2. The device of embodiment 1, wherein the array of microneedles is supported by an expandable band disposed around the mechanical actuator and configured to expand in response to expansion of the mechanical actuator.

[0162] Aspect 6. 1. A system comprising: A capsule, an interior surface defining an interior volume of the capsule; an outer surface sized to pass through a lumen defined by the lining of the digestive tract; and a carrier sized to fit within the interior volume of the capsule and supporting the array of microneedles; and a carrier for permitting the microneedles to penetrate the lining of the gastrointestinal tract. and a flexible, elastic material having flexibility that allows the mechanical actuator to contract away from an expanded state toward a contracted state that fits within an interior volume of the capsule, the flexible, elastic material further having elasticity that biases the mechanical actuator in a direction that expands outward from the contracted state toward the expanded state and that moves the carrier outward as the mechanical actuator overcomes or circumvents a constraint provided by the capsule.

[0163] Aspect 6A. The mechanical actuator includes a biasing member having a first end and a second end that can be folded toward each other, and a first end of the biasing member. 7. The system of embodiment 6, comprising: a holder hingedly attached and including a support surface for supporting the array of microneedles.

[0164] Aspect 7. The system of embodiment 6, wherein the capsule is configured to release the mechanical actuator from constraint on a portion of the digestive tract corresponding to the duodenum.

[0165] Aspect 8. The system of embodiment 7, wherein the capsule is configured to disintegrate in the duodenum to release the mechanical actuator from the constraint.

[0166] Aspect 9. 7. The system of embodiment 6, wherein the mechanical actuator and the carrier are each configured to move outward, away from a central longitudinal axis of the mechanical actuator.

[0167] Aspect 10. The system of embodiment 6, wherein the mechanical actuator comprises a collapsible tube compressible toward and expandable away from a central longitudinal axis of the mechanical actuator.

[0168] Aspect 11. The system of embodiment 10, 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.

[0169] Aspect 12. 7. The system of embodiment 6, wherein the mechanical actuator includes upper and lower cross beams joined by lateral columns having central hinges.

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

[0171] Aspect 14. 13. The system of embodiment 12, wherein the intermediate hinges pass each other when shifting between the contracted state and the expanded state.

[0172] Aspect 15. The system of embodiment 12, wherein the lateral columns include at least one set of two columns defining a slot therebetween, through which at least one of the lateral columns moves while shifting between a contracted state and an expanded state.

[0173] Aspect 16. The system of embodiment 6, wherein the mechanical actuator includes a coil having multiple overlapping turns that is wound more tightly in the contracted state than in the expanded state.

[0174] Aspect 17. The system of embodiment 6, wherein the mechanical actuator includes a plurality of curved arms attached at their proximal ends to a central core and movable such that their distal ends rotate in a spiral direction away from the core to move from a contracted state to an expanded state.

[0175] Aspect 18. The system of embodiment 6, wherein the mechanical actuator comprises a hub connected to a plurality of double-hinged arms, each double-hinged arm including (i) a first hinge connecting a 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 a distal portion of the double-hinged arm.

[0176] Aspect 19. 20. The system of embodiment 18, wherein in the contracted state, the proximal portion of the doubly hinged arm is positioned outward from the distal portion of the doubly hinged arm relative to a central longitudinal axis of the mechanical actuator.

[0177] Aspect 20. 19. The system of claim 18, wherein when moving from the contracted state to the expanded 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] Aspect 21. The system of embodiment 6, wherein the carrier comprises an expandable band disposed around the mechanical actuator.

[0179] Aspect 22. 7. The system of embodiment 6, wherein the array of microneedles is mechanically coupled to a mechanical actuator.

[0180] Aspect 23. 23. The system of embodiment 22, wherein the array of microneedles is integrally formed in the material of the mechanical actuator.

[0181] Aspect 24. The microneedle array Aspect ratio between 2 and 3, Pitch between 1.5mm and 2mm, and a sharpness of less than 1 micron.

[0182] Aspect 25. A method of treating a subject with a drug or biotherapeutic agent, comprising administering to the subject a device of embodiment 1, wherein the device comprises a drug or biotherapeutic payload.

[0183] Aspect 26. A method of treating a subject with a drug or biotherapeutic agent, comprising administering to the subject the system of embodiment 6, wherein the system comprises a drug or biotherapeutic payload.

[0184] Aspect 27. forming an assembly by coupling the array of microneedles with a mechanical actuator extendable outward from a central longitudinal axis; A method of making the assembly, comprising placing the assembly in a capsule having a first state that constrains the mechanical actuator from expanding, the capsule being reconfigurable at a target location within a subject to a second state in which the constraint by the capsule is released, allowing the mechanical actuator to expand to drive the array of microneedles into engagement with tissue at the target location.

[0185] Aspect 28. 28. The method of embodiment 27, further comprising forming an array of microneedles prior to coupling with the mechanical actuator.

[0186] Aspect 29. 28. The method of embodiment 27, wherein coupling the array of microneedles to the mechanical actuator comprises integrally forming the array of microneedles in a material of the mechanical actuator.

[0187] Aspect 30. 28. The method of embodiment 27, wherein coupling the array of microneedles with a mechanical actuator comprises disposing the mechanical actuator within an expandable band that supports the microneedles.

[0188] Aspect 31. Aspect ratio between 2 and 3 Pitch between 1.5mm and 2mm, or a sharpness of less than 1 micron.

[0189] In some aspects, a device, system, or method is provided according to one or more of the following examples, or some combination of elements thereof. In some aspects, a device or system described in one or more of these examples can be utilized to perform a method described in one of the other examples. Furthermore, features described with respect to a device or system can be implemented with respect to the method, and vice versa.

[0190] Example 1 1. A system comprising: A capsule, an interior surface defining an interior volume of the capsule; and a digestive tract. and an outer surface sized to pass through a lumen defined by an inner layer of the capsule. a carrier sized to fit within the interior volume of the capsule and supporting the array of microneedles; and a carrier for permitting the microneedles to penetrate the lining of the gastrointestinal tract. and a mechanical actuator operable to move the a collapsible biasing member including a first end and a second end, the first end and the second end comprising a flexible, resilient material having flexibility that allows the first end and the second end to fold toward each other to move from an expanded state toward a contracted state in which the mechanical actuator fits within the interior volume of the capsule, the flexible, resilient material further having resilience that urges the first end and the second end toward each other to move from the contracted state toward the expanded state and to move the carrier outward when the mechanical actuator overcomes or avoids a constraint provided by the capsule; a holder hingedly attached to the first end of the biasing member and including a support surface for supporting a carrier that carries an array of microneedles.

[0191] Example 2. The system of example 1, further comprising a linkage coupled to a first end of the folding biasing member.

[0192] Example 3. The system of Example 2, wherein the linkage includes a channel in which the holder is received in a contracted state to space the tips of the array of microneedles from the inner surface of the capsule.

[0193] Example 4. 3. The system of example 2, wherein the holder is hingedly attached to the first end of the biasing member via a hinge at least partially included in the linkage.

[0194] Example 5. 5. The system of example 4, further comprising a hinge stop surface included on the holder or linkage and positioned to prevent the hinge from rotating beyond a predetermined limit.

[0195] Example 6 The system described in example 1, wherein the collapsible biasing member comprises a nitinol wire.

[0196] Example 7 The system of example 1, wherein the foldable biasing member is a first foldable biasing member, and the holder is hingedly attached on a side facing the first foldable biasing member and the second foldable biasing member.

[0197] Example 8 The foldable biasing member and the holder include: a first holder and a second holder; a first link mechanism, a second link mechanism, a third link mechanism, and a fourth link mechanism; and a first collapsible biasing member and a second collapsible biasing member disposed within the assembly, such that: a first collapsible biasing member having opposing ends respectively received by the first link mechanism and the second link mechanism; a second collapsible biasing member having opposing ends respectively received by the third link mechanism and the fourth link mechanism; a first holder hingedly connected to the first link mechanism and the third link mechanism on opposing sides; The system of example 1, wherein the second holder is hingedly connected to the second linkage and the fourth linkage on opposing sides.

[0198] Example 9. The system of Example 1, wherein the holder is a first holder arranged to be attached to the second holder in a contracted state and having a removable attachment surface configured to release to allow the first holder and the second holder to be positioned symmetrically relative to each other.

[0199] Example 10. 10. The system of claim 1, comprising at least three holders interconnected by at least three collapsible biasing members each positioned to extend between laterally adjacent holders.

[0200] Example 11 1. A system comprising: A capsule, a first shell portion; a second shell portion; and an articulation portion for removably attaching the first shell portion to the second shell portion; an inner surface at least partially defined by the first shell portion and the second shell portion, the inner surface defining an interior volume of the capsule; and an inner surface at least partially defined by the first shell portion and the second shell portion, the inner surface sized to pass through a lumen defined by the lining of the digestive tract. a capsule comprising a shell having an outer surface; a carrier that is sized to fit within the interior volume of the capsule and that supports the array of microneedles and is operable to overcome or avoid the constraints provided by the articulation; a launcher operable to drive the first shell portion and the second shell portion away from the carrier to expose the array of microneedles.

[0201] Example 11A. 12. The system of example 11, wherein the launcher is operable to expose the array of microneedles to a position to achieve penetrating engagement with the lining of the gastrointestinal tract caused by peristaltic contractions of the gastrointestinal tract around the array of microneedles.

[0202] Example 12 12. The system of example 11, wherein the portions of the launcher are mounted within the first shell portion and the second shell portion, respectively, such that the portions of the launcher are retained therein after driving the first shell portion and the second shell portion away from the carrier.

[0203] Example 13 12. The system of claim 11, wherein the launcher comprises a coil spring arranged to press against a leverage surface of the core coupled to the carrier.

[0204] Example 14. 12. The system of example 11, wherein the first shell portion and the second shell portion include a groove shaped to receive a flange extending from the core coupled to the carrier to limit movement of the core within the capsule.

[0205] Example 15. The system of Example 11, wherein the carrier is attached to the core by a releasable bond in response to a release force less than a magnitude of a release force sufficient to release the array of microneedles from penetrating engagement with the lining of the gastrointestinal tract.

[0206] Example 16. 1. A system comprising a mechanical actuator configured for microneedle delivery, the mechanical actuator comprising a collapsible biasing member including a first end and a second end, a collapsible biasing member including a flexible, resilient material having flexibility that allows the first and second ends to fold toward each other to move from an expanded state toward a contracted state in which the mechanical actuator fits within a volume sized to fit within the ingestible capsule, the flexible, resilient material further having resilience that biases the first and second ends away from each other to move from the contracted state toward the expanded state; a holder hingedly attached to the first end of the biasing member and including a support surface configured to support a carrier carrying an array of microneedles, the support surface configured to support the carrier for outward movement to deploy the microneedles in response to movement from a contracted state toward an expanded state.

[0207] Example 17. 17. The system of Example 16, further comprising a carrier supporting the array of microneedles.

[0208] Example 18. The system of Example 16, further comprising a capsule.

[0209] Example 19. The foldable biasing member and the holder include: a first holder and a second holder; a first link mechanism, a second link mechanism, a third link mechanism, and a fourth link mechanism; and a first collapsible biasing member and a second collapsible biasing member disposed within the assembly, such that: a first collapsible biasing member having opposing ends respectively received by the first link mechanism and the second link mechanism; a second collapsible biasing member having opposing ends respectively received by the third link mechanism and the fourth link mechanism; a first holder hingedly connected to the first link mechanism and the third link mechanism on opposing sides; 17. The system of example 16, wherein the second holder is hingedly connected to the second link mechanism and the fourth link mechanism on opposing sides.

[0210] Example 20. A device comprising a capsule containing an array of microneedles and a launcher, the device in an ingestible form for delivery to the duodenum of a subject, wherein in response to a stimulus or condition within or during the duodenum, a first shell portion and a second shell portion of the capsule are released from one another, and the launcher drives the released first and second shell portions away from one another to expose the array of microneedles into a position to achieve penetrating engagement with the lining of the duodenum caused by peristaltic contractions of the lining around the exposed array of microneedles, the penetrating engagement facilitating delivery of a payload through the microneedles.

[0211] Reference to an embodiment or implementation herein means that a particular feature, structure, operation, or other characteristic described in connection with an embodiment can be included in at least one implementation of the present disclosure. The present disclosure is not limited to the particular embodiment or implementation so described. The appearance of the phrases "in one embodiment," "in an embodiment," "in one implementation," or "in an implementation," or variations thereof in various places herein, do not necessarily refer to the same embodiment or implementation. Any particular feature, structure, operation, or other characteristic described herein in connection with one embodiment or implementation may be combined with other features, structures, operations, or other characteristics described with respect to any other embodiment or implementation.

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

Claims

1. 1. A system comprising: A capsule, a first shell portion; a second shell portion; and an articulation portion for removably attaching the first shell portion to the second shell portion; an interior surface at least partially defined by the first shell portion and the second shell portion, the interior surface defining an interior volume of the capsule; a capsule including a shell having an outer surface at least partially defined by the first shell portion and the second shell portion, the outer surface sized to pass through a portion of the alimentary canal having an inner layer; a carrier sized to fit within the interior volume of the capsule and supporting an array of microneedles; a launcher operable to overcome or circumvent the constraint provided by the articulation and to actuate the first shell portion and the second shell portion to separate from the carrier and expose the array of microneedles; the first shell portion and the second shell portion include grooves shaped to receive flanges extending from a core coupled to the carrier to limit movement of the core within the capsule.

2. 10. The system of claim 1, wherein the launcher is operable to expose the array of microneedles in a position to achieve penetrating engagement with the inner layer of the gastrointestinal tract caused by peristaltic contractions of the gastrointestinal tract around the array of microneedles.

3. 2. The system of claim 1, wherein portions of the launcher are mounted within the first shell portion and the second shell portion, respectively, such that the portions of the launcher are retained therein after the actuation to separate the first shell portion and the second shell portion from the carrier.

4. The system of claim 1 , wherein the launcher comprises a coil spring positioned to press against a leverage surface of a core coupled to the carrier.

5. A system comprising: A capsule, a first shell portion; a second shell portion; and an articulation portion for removably attaching the first shell portion to the second shell portion; an interior surface at least partially defined by the first shell portion and the second shell portion, the interior surface defining an interior volume of the capsule; a capsule including a shell having an outer surface at least partially defined by the first shell portion and the second shell portion, the outer surface sized to pass through a portion of the alimentary canal having an inner layer; a carrier sized to fit within the interior volume of the capsule and supporting an array of microneedles; a launcher operable to overcome or circumvent the constraint provided by the articulation and to actuate the first shell portion and the second shell portion to separate from the carrier and expose the array of microneedles; The system, wherein the carrier is attached to the core by a releasable bond in response to a release force less than a magnitude of a release force sufficient to release the array of microneedles from penetrating engagement with the inner layer of the gastrointestinal tract.

Images