Devices and methods for delivering drugs through API-loaded tissue penetrators

Abstract

The drug delivery device includes at least one tissue-piercing member configured to be implanted in tissue, the at least one tissue-piercing member including: at least one cavity formed under an outer surface of the at least one tissue-piercing member, the at least one cavity having a depth from the outer surface and a width in a direction perpendicular to the direction of the depth from the outer surface; and at least one opening on the outer surface communicating with the at least one cavity such that at least one API loaded in the at least one cavity can be absorbed from the at least one cavity into the tissue, the width of the at least one opening being smaller than the width of the at least one cavity.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 483,241, filed February 3, 2023, the entire contents of which are incorporated herein by reference.

[0002] FIELD OF THE INVENTION The present disclosure relates generally to drug delivery devices, and more particularly to drug delivery devices in which an API is loaded onto a needle. [Background technology]

[0003] Microneedles and other tissue-penetrating devices are traditionally manufactured as monolithic structures, and any modification from that design relies on secondary processes (e.g., lathing, laser cutting, water jetting, etc.) to create features in the monolithic structure. These features can be used to deliver specific drug payloads or to provide sampling ports for fluidic diagnostic devices. These features are typically recessed from the monolithic structure because secondary processes are subtractive in nature. Furthermore, the features that can be fabricated prior to secondary processing are limited by current tissue-penetrating device manufacturing methods. Typical manufacturing methods include molding (e.g., cast molding, injection molding, loss-of-wax molding, etc.), lathing, and / or extrusion. Each of these methods limits the ability to include undercut features, negative draft structures, and internal channels.

[0004] Based on traditional manufacturing techniques, flexibility in loading drug payloads is limited by cavity feature size and / or the balance between mechanical and active pharmaceutical ingredient (API) properties (i.e., maintaining tissue penetration strength with needles composed of excipient and drug blends). For cavity feature size, there is typically minimal contact area between the drug payload and the needle device. The role of excipients on both needle adhesion and toughness limits selection and drug loading capabilities (i.e., increasing the excipient-to-drug ratio). Summary of the Invention

[0005] The drug delivery device includes at least one tissue penetrator that can be loaded with one or more APIs and delivers the one or more APIs to tissue when the tissue penetrator is implanted in the tissue. The tissue penetrator has multiple cavities for loading a payload containing one or more APIs. The payload can be a fluid solution, and the cavities can be configured to retain the fluid solution so that it does not flow out of the cavity before the tissue penetrator is implanted in the tissue. For example, the size of the opening through which the payload exits the cavity into the surrounding tissue can be configured based on the surface tension and viscosity of the fluid solution so that the fluid solution is retained within the cavity. The cavities can be interconnected below the surface of the tissue penetrator to increase the volume of the payload loading capacity while maintaining the ability to retain the fluid solution.

[0006] According to one aspect, a drug delivery device includes at least one tissue-piercing member configured to be implanted in tissue, the at least one tissue-piercing member including: at least one cavity formed below an outer surface of the at least one tissue-piercing member, the at least one cavity having a depth from the outer surface and a width in a direction perpendicular to the direction of the depth from the outer surface; and at least one opening on the outer surface communicating with the at least one cavity such that at least one API loaded in the at least one cavity can be absorbed from the at least one cavity into the tissue, wherein the width of the at least one opening is smaller than the width of the at least one cavity.

[0007] The at least one cavity may include a plurality of cavities, at least some of which are interconnected below the outer surface.

[0008] The at least one cavity may include at least one channel, and the at least one opening may include a longitudinally extending slot in the lengthwise direction of the at least one channel.

[0009] The at least one cavity may include a plurality of cavities arranged around a longitudinal axis of the at least one tissue-piercing member.

[0010] The drug delivery device may include a payload loaded into the at least one cavity, the payload including at least one API. Optionally, at least one of a surface tension and a viscosity of the payload is such that the payload remains within the at least one cavity before the at least one tissue-piercing member is embedded in the tissue. The payload may be 3D printed within the at least one cavity. The payload may have a total volume of at least 2 cubic millimeters.

[0011] The at least one tissue-piercing member may include a sharp tip for piercing tissue.

[0012] The at least one tissue-piercing member may have an outer diameter of up to 2 millimeters.

[0013] The at least one tissue-piercing member may include a plurality of microfluidic channels for holding at least a portion of the at least one API.

[0014] The at least one tissue-piercing member may be 3D printed using stereolithography or material jetting, or the like.

[0015] The at least one tissue-piercing member may be configured to be implanted within the stomach wall.The drug delivery device may be configured for oral administration.

[0016] According to one aspect, a method of delivering a drug to a tissue includes implanting at least one tissue-piercing member of a drug delivery device into tissue, the at least one tissue-piercing member including: at least one cavity formed below an outer surface of the at least one tissue-piercing member, the at least one cavity having a depth from the outer surface and a width in a direction perpendicular to the direction of the depth from the outer surface; and at least one opening on the outer surface communicating with the at least one cavity such that at least one API loaded in the at least one cavity can be absorbed into the tissue from the at least one cavity, wherein the width of the at least one opening is smaller than the width of the at least one cavity.

[0017] In the method, the drug delivery device may include any of the drug delivery devices described above.

[0018] According to one aspect, a drug delivery device includes at least one tissue-piercing member configured to be implanted in tissue, the at least one tissue-piercing member including a plurality of interconnecting cavities below an outer surface of the at least one tissue-piercing member, and a plurality of openings in the outer surface that communicate with the plurality of cavities such that at least one API loaded in the plurality of cavities can be absorbed into the tissue from the plurality of cavities.

[0019] The openings may be arranged about a longitudinal axis of the at least one tissue-piercing member.The openings may be arranged longitudinally of the at least one tissue-piercing member.

[0020] Optionally, a longitudinal axis of the at least one tissue-piercing member intersects with at least one cavity of the plurality of cavities.

[0021] The drug delivery device may include at least one payload including at least one API. Optionally, at least one of the surface tension and viscosity of the payload is such that the payload remains within the plurality of cavities before the at least one tissue-piercing member is embedded in the tissue. The payload may be 3D printed within the plurality of cavities. The payload may have a total volume of at least 2 cubic millimeters.

[0022] The at least one tissue-piercing member may include a sharp tip for piercing tissue.

[0023] The at least one tissue-piercing member may have an outer diameter of up to 2 millimeters.

[0024] The at least one tissue-piercing member may be 3D printed using stereolithography or material jetting, or the like.

[0025] The at least one tissue-piercing member may be configured to be implanted within the stomach wall.The drug delivery device may be configured for oral administration.

[0026] According to one aspect, a method of delivering a drug to tissue includes implanting at least one tissue-piercing member of a drug delivery device into tissue, the at least one tissue-piercing member including a plurality of interconnecting cavities below an outer surface of the at least one tissue-piercing member and a plurality of openings in the outer surface communicating with the plurality of cavities such that at least one API loaded in the plurality of cavities can be absorbed into the tissue from the plurality of cavities.

[0027] In the method, the drug delivery device may include any of the drug delivery devices described above. [Brief explanation of the drawings]

[0028] The invention will now be described, by way of example only, with reference to the accompanying drawings in which: [Figure 1A] 1 illustrates an exemplary tissue penetrator that includes a network of interconnected cavities for loading one or more APIs. [Figure 1B] 1 illustrates an exemplary tissue penetrator that includes a network of interconnected cavities for loading one or more APIs. [Figure 1C] 1 illustrates an exemplary tissue penetrator that includes a network of interconnected cavities for loading one or more APIs. [Figure 2A] 1A-1C show examples of tissue penetrators having larger cavities than the tissue penetrators of FIGS. 1A-1C. [Figure 2B] 1A-1C show examples of tissue penetrators having larger cavities than the tissue penetrators of FIGS. 1A-1C. [Figure 3A] 1A-1C and 2A-2B show examples of tissue penetrators having larger cavities than the tissue penetrators of FIGS. 1A-1C and 2A-2B. [Figure 3B] 1A-1C and 2A-2B show examples of tissue penetrators having larger cavities than the tissue penetrators of FIGS. 1A-1C and 2A-2B. [Figure 4A] 10 shows an example of a tissue penetrator with unconnected cavities. [Figure 4B] 10 shows an example of a tissue penetrator with unconnected cavities. [Figure 5] 1 shows an example of 3D printing of one or more tissue penetrators. [Figure 6] An example of 3D printing of a tissue penetrator is shown, where the payload is 3D printed within the cavity of the tissue penetrator. [Figure 7] 1 shows an example of an oral delivery device that includes at least one tissue penetrator. [Figure 8]1 shows an example of a microneedle device that includes multiple tissue penetrators extending from a substrate. DETAILED DESCRIPTION OF THE INVENTION

[0029] Described herein is a drug delivery device including a tissue penetrator that can be implanted into tissue to deliver one or more APIs to the tissue. The tissue penetrator can include multiple cavities that can be loaded with a payload including one or more APIs that are absorbed into the tissue when the tissue penetrator is implanted in the tissue. The payload can be a fluid solution (e.g., a low modulus gel, a viscous solution, etc.), and the cavities can be configured to retain the fluid solution so that it does not flow out of the cavity prior to use.

[0030] The outer surface of the tissue penetrator can have an opening formed therein that communicates with the cavity, allowing a payload loaded into the cavity to migrate into surrounding tissue when the tissue penetrator is implanted in the tissue. The size of the opening can be configured based on the characteristics of the fluid payload so that the fluid payload cannot prematurely escape through the opening. The cavity can extend below the outer surface of the tissue penetrator, for example, such that the width of the opening is greater than the corresponding width of the communicating cavity. In some embodiments, the cavities are interconnected below the outer surface of the tissue penetrator. For example, the cavities can form a mesh structure that helps retain a fluid solution within the cavity. The tissue penetrator can be fabricated by additive manufacturing, which may enable cavity configurations that are not achievable by subtractive manufacturing techniques.

[0031] Reference will now be made in detail to implementations and embodiments of the various aspects and variations of the devices, systems, and methods described herein. Although several exemplary variations of the devices, systems, and methods are described herein, other variations of the devices, systems, and methods may include aspects of the devices, systems, and methods described herein combined in any suitable manner, having all or some combination of the described aspects.

[0032] In the description that follows, it should be understood that the singular forms "a," "an," and "the," as used in the description that follows, are intended to include the plural forms as well, unless the context clearly indicates otherwise. The term "and / or," as used herein, should also be understood to refer to and include any and all possible combinations of one or more of the associated listed items. It should be further understood that the terms "includes," "including," "comprises," and / or "comprising," as used herein, specify the presence of stated features, integers, steps, operations, elements, components, and / or units, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, units, and / or groups thereof.

[0033] 1A-1C illustrate an exemplary tissue penetrator 100 including multiple cavities 102 for loading one or more payloads including one or more APIs. FIG. 1B is a cross-sectional view of the tissue penetrator 100 in a plane aligned with the longitudinal axis 101 of the tissue penetrator 100, and FIG. 1C is a cross-sectional view in a plane perpendicular to the longitudinal axis 101. The tissue penetrator 100 is configured to penetrate the surface of tissue and be embedded in the tissue. Once embedded in the tissue, the APIs loaded in the cavities 102 are absorbed by the surrounding tissue.

[0034] The tissue penetrator 100 includes a body 104 having a network of cavities 102 formed therein. The tip 106 can be configured to penetrate tissue, such as the skin or stomach lining. The tip 106 can be conical, as shown, or can include one or more bevels that form a sharply pointed tip. The body 104 can be straight, as shown, or curved or otherwise angled. The body 104 can have one or more barbs or other protruding features that help retain the tissue penetrator within tissue. The proximal end 116 of the body 104 can be attached or configured to be attached to the body of a drug delivery device (not shown), such as an intraorgan drug delivery device or an orthopedic implant. Multiple tissue penetrators 100 can be mounted on a substrate, such as a transdermal patch or surgical mesh, to simultaneously deliver one or more APIs at multiple locations.

[0035] A network of cavities 102 is formed within the body 104. The network of cavities 102 may extend through any desired portion of the body 104. For example, the network of cavities 102 may extend through the entire length of the body 104 or may extend through only a portion of the body 104, as shown in the embodiment of FIGS. 1A-1C. A payload may be loaded into the cavities 102 for delivery to tissue. The payload may include one or more APIs and, optionally, excipients. At least some of the cavities 102, such as cavities 102-A, 102-B, and 102-C in FIG. 1B, are located entirely below the surface 108 of the body 104. The cavities 102 may be interconnected with one another by interconnections 112 to form a three-dimensional interconnected network of cavities 102. Openings 110 are formed in the surface 108 of the body 104 and communicate with the cavities 102. One or more APIs loaded within the cavity 102 can be absorbed into the surrounding tissue through these openings 110 .

[0036] The configuration of the interconnected network of cavities 102 and the configuration of openings 110 may allow a substance having fluid-like properties (e.g., fluid-like properties at room temperature) to be retained within cavities 102. Examples of such fluid-like substances include low modulus gels, viscous solutions, semi-liquids, semi-solids, quasi-solids, pastes, etc. The openings 110 may be sized based on the viscosity and / or surface tension range of the desired fluid solution payload to be loaded into cavities 102 such that the fluid solution is restricted from flowing through the openings 110 except when absorbed by the surrounding tissue. The fluid solution payload may have a viscosity ranging from 5 to 300 cP, 300 to 3,000 cP, or 3,000 to 30,000 cP. The fluid solution payload may have a viscosity of at least 5 cP, at least 300 cP, at least 3,000 cP, or at least 30,000 cP. The fluid solution payload can have a viscosity of up to 5 cP, up to 300 cP, up to 3,000 cP, or up to 30,000 cP. The configuration of the multiple cavities 102 and their interconnections 112 can provide a relatively high surface area relative to the payload volume, which retards the flow of the fluid solution. The interconnections 112 can be sized to restrict flow between the cavities 102. For example, the interconnections 112 can have a smaller diameter than the cavities 102 they connect. In some embodiments, the network of interconnected cavities can retain the fluid solution.

[0037] As described above, at least some of the cavities 102 can be located completely below the surface 108 of the body 104. For example, with reference to FIG. 1B , there are three cavities 102-A, 102-B, and 102-C aligned in longitudinal positions that are located completely below the surface 108. As shown, a network of cavities 102 can extend through the thickness of the body 104. At least some of the cavities 102 can be located in the center of the body 104 so as to intersect the longitudinal axis 101 of the tissue penetrator 100. The cavities 102 can be any size and shape. For example, the cavities 102 can be spherical, tubular, cubic, irregular, oval, etc. The number and / or size of the cavities 102 can be selected based on the desired volume of the payload. In some embodiments, the cavities 102 may be twisted relative to the longitudinal axis 101 of the tissue penetrator 100, which may allow more cavities 102 to be formed within a cylindrical body, such as the body 104.

[0038] Any number of openings 110 can be formed in the surface 108 of the body 104. The number and / or size of the openings 110 can be selected to provide a desired amount of exposed surface area for one or more APIs loaded into the network of cavities 102 to be absorbed into the surrounding tissue to achieve a desired release profile of the one or more APIs. The openings 110 can be arranged around the longitudinal axis 101 of the tissue penetrator 100 and / or arranged in the longitudinal direction of the tissue penetrator 100. The openings 110 can be regularly spaced from one another in the longitudinal direction of the tissue penetrator 100 and / or regularly spaced from one another in the circumferential direction.

[0039] As discussed above, tissue penetrators can have cavities of any size and / or shape depending on the application. For example, a larger number of smaller cavities can be selected to hold less viscous solutions, and a smaller number of larger cavities can be selected to hold more viscous solutions or pastes. FIGS. 2A and 2B show an example of a tissue penetrator 200 that includes a network of larger cavities 202 (larger than cavities 102 in FIG. 1A) connected to each other via interconnects 212. FIG. 2B is a cross-sectional view taken along a plane including a longitudinal axis 201. Relative to tissue penetrator 100, tissue penetrator 200 includes larger openings 210 that communicate with the network of cavities 202. These larger openings 210 provide a larger payload-to-tissue contact surface area, which may result in faster absorption of one or more APIs. FIGS. 3A and 3B show an example of a tissue penetrator 300 that includes a network of even larger cavities 302. FIG. 3B is a cross-sectional view taken along a plane including a longitudinal axis 301. In the illustrated example, there are two cavities 302 that extend in a spiral shape around the longitudinal axis 301. An opening 310 in a surface 308 of the body 304 in which the cavities 302 are formed follows the spiral shape of the cavities 302. In contrast to the tissue penetrator 100 of Figures 1A-1C, the tissue penetrator 300 can be used with payload materials that are solid or more solid-like than the payload materials used in the tissue penetrator 100.

[0040] The tissue penetrators of Figures 1A-3B include a network of interconnected cavities designed to retain a fluidic payload within the cavities. Figures 4A and 4B illustrate an alternative configuration of cavities for retaining a fluidic payload in a tissue penetrator in which the cavities are not interconnected. The tissue penetrator 400 of Figures 4A and 4B includes multiple non-interconnected cavities 402 formed within the body 404 of the tissue penetrator 400. Openings 410 are formed in a surface 408 of the body 404 that communicate with the cavities 402. The openings 410 are sized smaller than the size of the cavities 402 to prevent the desired payload from escaping from the cavities 402 before being embedded in the tissue.

[0041] In the illustrated example, the cavities 402 are channel-shaped and have their longitudinal direction extending longitudinally of the tissue penetrator 400. In other examples, the cavities 402 extend circumferentially around the longitudinal axis 401 of the tissue penetrator 400 or are twisted relative to the longitudinal axis 401 of the tissue penetrator 400. The cavities 402 may extend along a portion of the tissue penetrator 400 and may stop short of the end of the tissue penetrator 400 so that the cavities 402 do not break off at their end through the surface 408 of the tissue penetrator, further ensuring that the payload does not exit the cavities 402 prematurely.

[0042] The openings 410 can extend longitudinally as shown, and can extend the entire length of the cavity 402, or only a portion of the length of the cavity 402. The openings 410 for each cavity 402 can be continuous, as shown, or there can be multiple discrete openings for each cavity 402. The width of the openings 410 is smaller than the width of the cavity 402 (the maximum size of the cavity in a direction perpendicular to the depth of the cavity from the outer surface 408 of the body 404) such that the outer surface 408 of the body 404 extends over a portion of the cavity. In other words, when viewed radially outward from the cavity 102, the cavity 102 is below and partially covered by, for example, the wall 420 of the body 404. The width of the openings 410 can be selected based on the characteristics of the desired payload, such that, for example, the surface tension and viscosity of the payload prevent the payload from flowing through the openings 410.

[0043] The number, size, and shape of the cavities 402 can be selected based on the desired payload capacity, payload characteristics, and / or size of the tissue penetrator 400. In the illustrated example, the cavities 402 are evenly arranged about the longitudinal axis 401, however, it should be understood that any arrangement of the cavities 402 can be used to meet the requirements of a desired application. The cavities 402 can be isolated from one another, as shown in FIGS. 4A and 4B , or can be interconnected to one another beneath the outer surface 408 of the body 404. In some embodiments, the cavities 402 are microfluidic channels.

[0044] In some embodiments, the tissue penetrator can include multiple different cavity configurations, such as to accommodate different types of payloads. For example, the tissue penetrator can have a network of smaller cavities for loading a first payload having a lower viscosity and a network of larger cavities for loading a second payload having a higher viscosity. This arrangement allows the same tissue penetrator to be used to provide delivery of different APIs, different amounts of API, and / or different release rates of API. The different cavity networks can be located in different sections of the tissue penetrator.

[0045] The tissue penetrator can be sized according to a given application, such as to achieve a desired penetration depth and / or to achieve a desired total payload volume. For example, multiple relatively small tissue penetrators, often referred to as microneedles, can be mounted on a patch and pressed into the skin for API delivery into the skin, such as below the stratum corneum, a relatively large tissue penetrator can be constructed into an oral delivery device for implantation into the stomach lining, and an even larger tissue penetrator can be configured for orthopedic applications in which the tissue penetrator is implanted into bone. The tissue penetrator can have a wide range of different diameters. For example, the tissue penetrator can have a diameter corresponding to the diameter of a standard hypodermic needle gauge. For example, tissue penetrators have dimensions of approximately 4.57mm, 4.19mm, 3.76mm, 3.40mm, 3.05mm, 2.77mm, 2.41mm, 2.11mm, 1.83mm, 1.65mm, 1.47mm, 1.27mm, 1.07mm, 0.91mm, 0.82mm, 0.72mm, 0.64mm, 0.57mm, 0.51mm, 0.46mm, 0.41mm, and 0. The tissue penetrator can have a diameter corresponding to a hypodermic needle gauge of 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, or 34, which corresponds to an outer diameter of 36 mm, 0.34 mm, 0.31 mm, 0.26 mm, 0.24 mm, 0.21 mm, or 0.18 mm. Thus, the tissue penetrator can have an outer diameter of up to 5 mm, e.g., up to 4.5 mm, up to 4 mm, up to 3.5 mm, up to 3 mm, up to 2.5 mm, up to 2 mm, up to 1.5 mm, up to 1 mm, or up to 0.5 mm. The length of the tissue penetrator (as measured from the distal end to the proximal end that is attached or attachable to a support structure) can be less than 20 mm, less than 15 mm, less than 10 mm, less than 5 mm, less than 1 mm, or less than 0.5 mm. The length of the tissue penetrator can be at least 0.1 mm, at least 0.5 mm, at least 1 mm, at least 5 mm, or at least 10 mm.

[0046] The size of the tissue penetrator, the number and size of the cavities in the tissue penetrator, can be selected to achieve a total cavity volume that provides the desired total volume of the payload. For example, the tissue penetrator can have a cavity size of at least 0.5 mm. 3 , at least 1 mm 3 , at least 1.5 mm 3 , at least 2 mm 3 , at least 2.5 mm 3 , at least 3 mm 3 , at least 3.5mm 3 , at least 4 mm 3 , at least 4.5mm 3 , or at least 5 mm 3 The tissue penetrator can be configured for a total payload volume of 10 mm. 3 Below, 8mm 3 Below, 6mm 3 or less, or 4 mm 3 It can be configured for the following total payload volumes:

[0047] The openings on the exterior surface of the tissue penetrator can be configured to provide a desired total payload-to-tissue contact area (the area of ​​the payload loaded within the cavity that is exposed to the exterior and available for contact with tissue) for a given application, such as to achieve a desired API release profile. The total payload-to-tissue contact area is at least 1 mm 2 , at least 5 mm 2 , at least 10 mm 2 , at least 15mm 2 , at least 20 mm 2 , at least 30mm 2 , or at least 50 mm 2 The total payload-to-tissue contact area can be up to 100 mm 2 , up to 50mm 2 , up to 30mm 2 , up to 20mm 2 , or a maximum of 10 mm 2 It could be.

[0048] According to various embodiments, tissue penetrators are fabricated using one or more additive manufacturing processes. For example, the network of cavities 102 of tissue penetrator 100 of FIGS. 1A-1C cannot be formed using subtractive manufacturing techniques and is therefore formed using additive manufacturing. FIG. 5 illustrates an example of forming a tissue penetrator using additive manufacturing. One or more tissue penetrators 500 (which may include any of tissue penetrators 100, 200, 300, and 400) can be constructed on substrate 550 using a 3D printing system 580. Suitable 3D printing systems can include stereolithography, material jetting systems, binder jetting systems, and powder bed fusion systems. Cavities 502 can be formed by an additive manufacturing process, which can enable the formation of a much wider range of cavity shapes and sizes than is achievable or practical using other manufacturing techniques, such as subtractive manufacturing or molding techniques. For example, undercut features, interconnected cavities below the surface of the tissue penetrator, and / or microfluidic channels are features that can be formed in the tissue penetrator using additive manufacturing that may not be possible using other manufacturing techniques.

[0049] In some embodiments, the payload is formed within the cavities during an additive manufacturing process. Figure 6 shows an example of 3D printing of tissue penetrator 600, where payload 604 is 3D printed within cavity 602 simultaneously with the formation of cavity 602. 3D printing of payloads may allow different types of payloads to be deposited into different cavities of the same tissue penetrator. For example, payload 604 may be 3D printed within a first set of cavities, and a different type of payload 606 may be 3D printed within a second set of cavities 608.

[0050] As described above, various embodiments of tissue penetrators can be incorporated into various drug delivery devices for a variety of different applications. FIG. 7 shows an example of an oral delivery device 700 including at least one tissue penetrator 702 for delivering one or more APIs to tissue 760 of the gastrointestinal tract, such as the stomach lining. The tissue penetrator 702 can be any of tissue penetrators 100, 200, 300, and 400. The oral delivery device 700 can include a body 750 to which the tissue penetrator 702 is connected. The body 750 can be configured for oral administration and can be configured to be carried by the gastrointestinal tract to a desired location where the tissue penetrator is pushed into the tissue. In some embodiments, the body 750 includes a mechanical actuator 752, driven by, for example, a spring positioned within the body 750, that pushes the tissue penetrator 702 into the tissue. In some embodiments, the tissue penetrator 702 is stored within the body 750 and deployed at a desired time or when the desired location is reached. For example, the body 750 may include a dissolvable catch that, when dissolved via interaction with stomach acid, releases an actuator that deploys one or more tissue penetrators 702. The tissue penetrators 702 may be configured to passively detach from the tissue after a period of time, or may be configured to dissolve over a period of time.

[0051] 8 shows an example of a microneedle device 800 including multiple tissue penetrators 802 extending from a substrate 850 for implantation into tissue 860. The tissue penetrators 802 may be one or more of tissue penetrators 100, 200, 300, and 400. The microneedle device 800 may be, for example, a patch, an orthoplate, or a hydrogel. The device 800 may be, for example, a patch that is pressed onto a patient's skin to deliver one or more APIs loaded into the multiple tissue penetrators below the skin surface. The patch may be manually removed after a sufficient period of time has passed for the one or more APIs to be absorbed into the tissue.

[0052] The tissue penetrator may be incorporated into a surgical staple, for example, incorporated into or may form the penetrating end of the surgical staple. The tissue penetrator may be configured to carry an API designed to improve wound closure and healing. The tissue penetrator may be loaded into a device (e.g., a handheld device) that drives the tissue penetrator into tissue by spring action or the like. For example, a user can position the delivery end of the device at a desired location on a patient and actuate the device (e.g., by pressing a button or pulling a trigger), which can drive the tissue penetrator into tissue to a desired depth.

[0053] The tissue penetrator may be (or may be incorporated into) an implantable rod for oncology treatment. The tissue penetrator may be (or may be incorporated into) an orthopedic screw, a femoral nail, and / or a tendon fixation device.

[0054] In some embodiments, the tissue penetrator may be made of (or may include) a metal, a ceramic material, or a polymeric material. The tissue penetrator material may be (or may include) silicon, or a metal or metal alloy such as stainless steel, titanium, magnesium alloy, or nickel-titanium alloy. Exemplary types of medical-grade polymeric materials include polycarbonate, liquid crystal polymer (LCP), polyetheretherketone (PEEK), cyclic olefin copolymer (COC), and polybutylene terephthalate (PBT).

[0055] In some embodiments, the tissue penetrator material can be (or can include) a biodegradable polymeric material. Exemplary types of medical-grade biodegradable materials include polylactic acid (PLA), polyglycolic acid (PGA), copolymers of PGA and PLA, and polyesteramide polymers (PEA).

[0056] In some embodiments, the tissue penetrator material may be (or may include) absorbable polyurethane, polycaprolactone (PCL), polydioxanone (PDO), propylene fumarate (PPF), poly(trimethylene carbonate) (PTMC), combinations thereof, and copolymers thereof with PLA and / or PGA.

[0057] In some embodiments, the tissue penetrator material may be (or may include) a light-curable resin composed of (meth)acrylate-terminated absorbable polyester oligomers.

[0058] In some embodiments, the tissue penetrator, or portions thereof, may be made from a dissolvable or degradable material. The dissolvable or degradable material may be any solid material that dissolves or degrades during use. For example, the tissue penetrator may be made to sufficiently dissolve or degrade in the tissue in which it is embedded. In some embodiments, the dissolvable or degradable material is selected from a carbohydrate or sugar. In some embodiments, the dissolvable or degradable material is polyvinylpyrrolidone (PVP). In some embodiments, the dissolvable or degradable material is selected from the group consisting of hyaluronic acid, carboxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinyl alcohol, sucrose, glucose, dextran, trehalose, maltodextrin, and any combination thereof.

[0059] Although tissue penetrating devices are described above as being for delivering an API into tissue, tissue penetrating devices may be configured with multiple cavities in accordance with the principles described herein for obtaining samples from tissue. For example, a tissue penetrating device without any cavities can be inserted into tissue, and cells, fluids, and / or other substances present in the tissue may migrate into the cavities. The tissue penetrating device can then be extracted from the tissue, and the sample can be used for diagnostic purposes, etc.

[0060] In some embodiments, the tissue penetrator or a portion thereof may include a contrast agent to enable visualization of the tissue penetrator by an imaging system, which may be useful for confirming placement of the tissue penetrator in applications where the tissue penetrator penetrates tissue within the body. The contrast agent may be, for example, a contrast agent that can be detected by a fluoroscopic imaging system. In some embodiments, the contrast agent is a component of a material forming at least a portion of the body 104 of the tissue penetrator 100 of FIG. 1A. For example, the contrast agent may be a component of a 3D printing material used to 3D print the tissue penetrator. Additionally or alternatively, the contrast agent may be loaded into one or more cavities of the tissue penetrator. For example, the contrast agent may be loaded into a set of one or more cavities, and a payload having one or more APIs may be loaded into a different set of one or more cavities, and the loading may be performed using a 3D printing process.

[0061] The foregoing description has been set forth with reference to specific embodiments for purposes of explanation. However, the illustrative discussion above is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the technology and their practical applications, thereby enabling others skilled in the art to best utilize the technology and various embodiments, with various modifications as suited to the particular use contemplated.

[0062] Although the present disclosure and examples have been fully described with reference to the accompanying drawings, it should be noted that various changes and modifications will become apparent to those skilled in the art. Such changes and modifications are to be understood as being included within the scope of the present disclosure and examples as defined by the claims. Finally, the entire disclosures of the patents and publications mentioned in this application are incorporated herein by reference.

Claims

1. 1. A drug delivery device comprising: at least one tissue-piercing member configured to be implanted in tissue, the at least one tissue-piercing member comprising: at least one cavity formed below an outer surface of the at least one tissue-piercing member, the at least one cavity having a depth from the outer surface and a width in a direction perpendicular to the direction of the depth from the outer surface; and at least one opening on the outer surface communicating with the at least one cavity such that at least one API loaded in the at least one cavity can be absorbed into the tissue from the at least one cavity, wherein a width of the at least one opening is smaller than the width of the at least one cavity.

2. The drug delivery device of claim 1 , wherein the at least one cavity comprises a plurality of cavities, at least some of the cavities being interconnected beneath the outer surface.

3. 3. The drug delivery device of claim 1, wherein the at least one cavity comprises at least one channel, and the at least one opening comprises a slot extending longitudinally in the longitudinal direction of the at least one channel.

4. The drug delivery device of any one of claims 1 to 3, wherein the at least one cavity comprises a plurality of cavities arranged around a longitudinal axis of the at least one tissue-piercing member.

5. The drug delivery device of any one of claims 1 to 4, wherein the drug delivery device comprises a payload loaded in the at least one cavity, the payload comprising the at least one API.

6. The drug delivery device of claim 5, wherein at least one of the surface tension and viscosity of the payload is such that the payload remains within the at least one cavity before the at least one tissue-piercing member is embedded in the tissue.

7. 7. The drug delivery device of claim 5 or 6, wherein the payload is 3D printed within the at least one cavity.

8. The drug delivery device according to any one of claims 5 to 7, wherein the payload has a total volume of at least 2 cubic millimeters.

9. The drug delivery device of any one of claims 1 to 8, wherein the at least one tissue-piercing member comprises a sharp tip for piercing the tissue.

10. The drug delivery device of any one of claims 1 to 9, wherein the at least one tissue-piercing member has an outer diameter of up to 2 millimeters.

11. The drug delivery device of any one of claims 1 to 10, wherein the at least one tissue-piercing member comprises a plurality of microfluidic channels for holding at least a portion of the at least one API.

12. The drug delivery device of any one of claims 1 to 11, wherein the at least one tissue-piercing member is 3D printed.

13. The drug delivery device of claim 12 , wherein the at least one tissue-piercing member is 3D printed using stereolithography or material jetting.

14. The drug delivery device of any one of claims 1 to 13, wherein the tissue is the stomach wall.

15. The drug delivery device of any one of claims 1 to 14, wherein the drug delivery device is configured for oral administration.

16. 1. A method of delivering a drug to a tissue, the method comprising:

1. A method comprising: embedding at least one tissue-piercing member of a drug delivery device into the tissue, wherein the at least one tissue-piercing member comprises: at least one cavity formed below an outer surface of the at least one tissue-piercing member, the at least one cavity having a depth from the outer surface and a width in a direction perpendicular to the direction of the depth from the outer surface; and at least one opening in the outer surface communicating with the at least one cavity such that at least one API loaded in the at least one cavity can be absorbed into the tissue from the at least one cavity, wherein the width of the at least one opening is smaller than the width of the at least one cavity.

17. The method of claim 16, wherein the drug delivery device comprises a drug delivery device according to any one of claims 2 to 15.

18. 1. A drug delivery device comprising: at least one tissue-piercing member configured to be implanted in tissue, the at least one tissue-piercing member comprising: a plurality of interconnected cavities beneath an outer surface of the at least one tissue-piercing member; a plurality of openings in the outer surface communicating with the plurality of cavities such that at least one API loaded in the plurality of cavities can be absorbed from the plurality of cavities into the tissue.

19. 20. The drug delivery device of claim 18, wherein the openings are arranged about a longitudinal axis of the at least one tissue-piercing member.

20. 20. The drug delivery device of claim 18 or 19, wherein the openings are aligned longitudinally of the at least one tissue-piercing member.

21. The drug delivery device of any one of claims 18 to 20, wherein the longitudinal axis of the at least one tissue-piercing member intersects with at least one cavity of the plurality of cavities.

22. The drug delivery device of any one of claims 18 to 21, wherein the drug delivery device comprises at least one payload comprising the at least one API.

23. 23. The drug delivery device of claim 22, wherein at least one of the surface tension and viscosity of the payload is such that the payload remains within the plurality of cavities before the at least one tissue-piercing member is embedded in the tissue.

24. 24. The drug delivery device of claim 22 or 23, wherein the payload is 3D printed within the plurality of cavities.

25. The drug delivery device of any one of claims 22 to 24, wherein the payload has a total volume of at least 2 cubic millimeters.

26. The drug delivery device of any one of claims 18 to 25, wherein the at least one tissue-piercing member comprises a sharp tip for piercing the tissue.

27. The drug delivery device of any one of claims 18 to 26, wherein the at least one tissue-piercing member has an outer diameter of up to 2 millimeters.

28. The drug delivery device of any one of claims 18 to 27, wherein the at least one tissue-piercing member is 3D printed.

29. 30. The drug delivery device of claim 28, wherein the at least one tissue-piercing member is 3D printed using stereolithography or material jetting.

30. The drug delivery device of any one of claims 18 to 29, wherein the tissue is the stomach wall.

31. The drug delivery device of any one of claims 18 to 30, wherein the drug delivery device is configured for oral administration.

32. 1. A method of delivering a drug to a tissue, the method comprising:

1. A method comprising: implanting at least one tissue-piercing member of a drug delivery device into the tissue, the at least one tissue-piercing member comprising a plurality of interconnected cavities beneath an outer surface of the at least one tissue-piercing member; and a plurality of openings in the outer surface communicating with the plurality of cavities such that at least one API loaded in the plurality of cavities can be absorbed from the plurality of cavities into the tissue.

33. The method of claim 32, wherein the drug delivery device comprises a drug delivery device according to any one of claims 19 to 31.

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