EP4658353A1

EP4658353A1 - Devices and methods for delivering a drug via an api-loaded tissue penetrator

Info

Publication number: EP4658353A1
Application number: EP24751073.8A
Authority: EP
Inventors: Peyton HOPSON; Stephen G. Gara; Drake SMALLEY
Original assignee: Janssen Biotech Inc
Current assignee: Janssen Biotech Inc
Priority date: 2023-02-03
Filing date: 2024-02-02
Publication date: 2025-12-10
Also published as: CN120603620A; WO2024163828A1; JP2026504446A

Abstract

A drug delivery device includes at least one tissue penetrating member configured to embed into tissue, the at least one tissue penetrating member including at least one cavity formed beneath an outer surface of the at least one tissue penetrating member, the at least one cavity having a depth from the outer surface and a width in a direction that is orthogonal to a direction of the depth from the outer surface, and at least one opening in the outer surface that communicates with the at least one cavity so that at least one API loaded into the at least one cavity can be absorbed from the at least one cavity into the tissue, wherein a width of the at least one opening is less than the width of the at least one cavity.

Description

DEVICES AND METHODS FOR DELIVERING A DRUG VIA AN API-LOADED TISSUE PENETRATOR

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63/483,241, filed February 3, 2023, the entire contents of which are hereby incorporated by reference herein.

FIELD

[0002] 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

[0003] Microneedles, and other tissue penetrating devices, have been traditionally manufactured in monolithic-type structures with any modification from that design dependent on secondary processing (e.g., lathing, laser cutting, water jetting, etc.) to produce features in the monolithic- type structures. These features can be used to carry a specific drug payload or provide sampling ports for fluidic diagnostic devices. These features are typically recessed from the monolithic structure as the secondary processing is subtractive in nature. Additionally, features that can be fabricated before secondary processing are limited by current tissue penetrating device manufacturing methods. Typical manufacturing methods include molding (e.g., cast molding, injection molding, loss wax molding, etc.), lathing, and/or extrusion processing. Each of these methods limit the ability to have undercut features, negative draft angle structures, and internal channels.

[0004] Based on conventionally used manufacturing techniques, flexibility in loading the drug payload is limited by cavity feature size and/or balance of mechanical properties and drug active pharmaceutical ingredient (API) properties (i.e., retaining tissue penetration strength with needles comprised of excipient and drug blend). In case of cavity feature size, there is typically minimal contact area between the drug payload and needle device. The role of excipient for both adherence to the needle and toughness limits the choice and drug loading capability (i.e., increased excipient to drug ratio). SUMMARY

[0005] A drug delivery device includes at least one tissue penetrator that can be loaded with one or more APIs for delivering the one or more APIs to tissue when the tissue penetrator is embedded in the tissue. The tissue penetrator has a plurality of cavities for loading with payload that includes the one or more APIs. The payload can be a fluid-like solution, and the cavities can be configured to retain the fluid-like solution so that the fluid-like solution does not flow out of the cavities before the tissue penetrator is embedded in tissue. For example, sizes of openings through which the payload exits the cavities to surrounding tissue can be configured based on the surface tension and viscosity of the fluid-like solution so that the fluid-like solution is retained in the cavities. The cavities can interconnect beneath a surface of the tissue penetrator to increase the volume of payload loading capacity while preserving the ability to retain the fluid-like solution.

[0006] According to an aspect, a drug delivery device includes at least one tissue penetrating member configured to embed into tissue, the at least one tissue penetrating member including at least one cavity formed beneath an outer surface of the at least one tissue penetrating member, the at least one cavity having a depth from the outer surface and a width in a direction that is orthogonal to a direction of the depth from the outer surface, and at least one opening in the outer surface that communicates with the at least one cavity so that at least one API loaded into the at least one cavity can be absorbed from the at least one cavity into the tissue, wherein a width of the at least one opening is less than the width of the at least one cavity.

[0007] The at least one cavity may include a plurality of cavities and at least some of the cavities interconnect beneath the outer surface.

[0008] The at least one cavity may include at least one channel and the at least one opening may include a slot that extends longitudinally in a longitudinal direction of the at least one channel.

[0009] The at least one cavity may include a plurality of cavities that are arrayed around a longitudinal axis of the at least one tissue penetrating member.

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

[0011] The at least one tissue penetrating member may include a pointed tip for piercing the tissue.

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

[0013] The at least one tissue penetrating 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 penetrating member may be 3D printed, such as using stereolithography or material jetting.

[0015] The at least one tissue penetrating member may be configured to embed into a stomach wall. The drug delivery device may be configured for oral administration.

[0016] According to an aspect, a method of delivering a drug to tissue includes embedding at least one tissue penetrating member of a drug delivery device into the tissue, the at least one tissue penetrating member comprising at least one cavity formed beneath an outer surface of the at least one tissue penetrating member, the at least one cavity having a depth from the outer surface and a width in a direction that is orthogonal to a direction of the depth from the outer surface, and at least one opening in the outer surface that communicates with the at least one cavity so that at least one API loaded into the at least one cavity can be absorbed from the at least one cavity into the tissue, wherein a width of the at least one opening is less 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 above.

[0018] According to an aspects, a drug delivery device includes at least one tissue penetrating member configured to embed into tissue, the at least one tissue penetrating member including a plurality of cavities that interconnect beneath an outer surface of the at least one tissue penetrating member, and a plurality of openings in the outer surface that communicate with the plurality of cavities so that at least one API loaded into the plurality of cavities can be absorbed from the plurality of cavities into the tissue. [0019] The openings may be arrayed about a longitudinal axis of the at least one tissue penetrating member. The openings may be arrayed in a longitudinal direction of the at least one tissue penetrating member.

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

[0021] The drug delivery device may include at least one payload that comprises the at least one API. Optionally, at least one of a surface tension and a viscosity of the payload is such that the payload remains in the plurality of cavities prior to the at least one tissue penetrating member embedding into the tissue. The payload may be 3D printed into the plurality of cavities. The payload may have a total volume of at least 2 cubic millimeters.

[0022] The at least one tissue penetrating member may include a pointed tip for piercing the tissue.

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

[0024] The at least one tissue penetrating member may be 3D printed, such as using stereolithography or material jetting.

[0025] The at least one tissue penetrating member may be configured to embed into a stomach wall. The drug delivery device may be configured for oral administration.

[0026] According to an aspect, a method of delivering a drug to tissue includes embedding at least one tissue penetrating member of a drug delivery device into the tissue, the at least one tissue penetrating member comprising a plurality of cavities that interconnect beneath an outer surface of the at least one tissue penetrating member, and a plurality of openings in the outer surface that communicate with the plurality of cavities so that at least one API loaded into the plurality of cavities can be absorbed from the plurality of cavities into the tissue.

[0027] In this method, the drug delivery device may include any of the above drug delivery devices. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0029] FIGS. 1 A-C illustrate an exemplary tissue penetrator that includes a network of interconnected cavities for loading with one or more APIs;

[0030] FIGS. 2A and 2B illustrate an example of a tissue penetrator that has larger cavities than the tissue penetrator of FIGS. 1A-C;

[0031] FIGS. 3A and 3B illustrate an example of a tissue penetrator that has larger cavities than the tissue penetrators of FIGS. 1A-C and FIG. 2A and 2B;

[0032] FIGS. 4A and 4B illustrate an example of a tissue penetrator that has unconnected cavities;

[0033] FIG. 5 illustrates an example of 3D printing of one or more tissue penetrators;

[0034] FIG. 6 illustrates an example of the 3D printing of a tissue penetrator in which a payload is 3D printed into the cavities of the tissue penetrator;

[0035] FIG. 7 illustrates an example of an oral delivery device that includes at least one tissue penetrator; and

[0036] FIG. 8 illustrates an example of a microneedle device that includes a plurality of tissue penetrators that extend from a substrate.

DETAILED DESCRIPTION

[0037] Described herein are drug delivery devices that include tissue penetrators that can embed in tissue to deliver one or more APIs to the tissue. The tissue penetrators can include a plurality of cavities that can be loaded with payload that includes one or more APIs that absorb into tissue when the tissue penetrators are embedded in the tissue. The payload can be a fluid-like solution (e.g., low modulus gels, viscous solutions, etc.), and the cavities can be configured to retain the fluid-like solution so that the fluid-like solution does not flow out of the cavities before use. [0038] Openings can be formed in the external surface of the tissue penetrator that communicate with the cavities so that payload loaded in the cavities can migrate into surrounding tissue when the tissue penetrator is embedded in tissue. The sizes of the openings can be configured based on properties of the fluid-like payload such that the fluid-like payload cannot flow out through the openings prematurely. The cavities can extend beneath the external surface of the tissue penetrator such that, for example, a width of an opening is greater than a corresponding width of the cavity with which it communicates. In some embodiments, the cavities interconnect beneath the external surface of the tissue penetrator. For example, the cavities can form a mesh structure that helps retain fluid-like solutions in the cavities. Tissue penetrator can be made via additive manufacturing, which can enable cavity configurations not achievable via subtractive manufacturing techniques.

[0039] Reference will now be made in detail to implementations and embodiments of various aspects and variations of 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 combinations of all or some of the aspects described.

[0040] In the following description, it is to be understood that the singular forms “a,” “an,” and “the” used in the following description are intended to include the plural forms as well, unless the context clearly indicates otherwise. It is also to be understood that the term “and/or” as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. It is further to be understood that the terms “includes, “including,” “comprises,” and/or “comprising,” when used herein, specify the presence of stated features, integers, steps, operations, elements, components, and/or units but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, units, and/or groups thereof.

[0041] FIGS. 1A-1C illustrate an exemplary tissue penetrator 100 that includes a plurality of cavities 102 for loading with one or more payloads that include one or more APIs. FIG. IB is a cross section of the tissue penetrator 100 on a plane aligned with a longitudinal axis 101 of the tissue penetrator 100 and FIG. 1C is a cross section on a plane perpendicular to the longitudinal axis 101 . The tissue penetrator 100 is configured to penetrate a surface of tissue and embed into the tissue. When embedded in the tissue, API loaded in the cavities 102 absorbs into the surrounding tissue.

[0042] The tissue penetrator 100 includes a body 104 into which a network of cavities 102 are formed. A tip 106 can be configured for penetrating into tissue, such as into the skin or stomach lining. The tip 106 can be conical in shape, as illustrated, or can include one or more bevels that form a sharp pointed tip. The body 104 can be straight as illustrated or can be curved or otherwise angled. The body 104 can have one or more barbs or other projecting features that help retain the tissue penetrator in the tissue. The proximal end 116 of the body 104 can be attached to or configured for attachment to a main body (not shown) of a drug delivery device, such as an intraorgan drug delivery device or an orthopedic implant. A plurality of tissue penetrators 100 can be mounted to a substrate, such as a transdermal patch or a surgical mesh, for simultaneously delivering one or more APIs at multiple locations.

[0043] The network of cavities 102 are formed in the body 104. The network of cavities 102 can extend through any desired portion of the body 104. For example, the network of cavities 102 can extend through an entire length of the body 104 or can extend through just a portion of the body 104, as illustrated in the embodiment of FIGS. 1A-C. Payload can be loaded into the cavities 102 for delivery to the tissue. The payload can include one or more APIs and, optionally, excipient. At least some of the cavities 102 are located entirely beneath a surface 108 of the body 104, such as cavities 102-A, 102-B, and 102-C of FIG. IB. The cavities 102 may be interconnected to one another by interconnections 112, forming 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 into the cavities 102 can absorb into surrounding tissue through these openings 110.

[0044] The configuration of the interconnected network of cavities 102 and the configuration of the openings 110 can enable the retention of substances that have fluid-like properties (e.g., fluidlike properties at room temperature) in the cavities 102. Examples of such fluid-like substances include low modulus gels, viscous solutions, semifluids, semisolids, quasi-solids, pastes, etc. The openings 110 can be sized based on the range of viscosities and/or surface tensions of the desired fluid-like solution payloads to be loaded in the cavities 102 such that the fluid-like solutions are restricted from flowing out through the openings 110 except when being absorbed into surrounding tissue. The fluid-like solution payloads may have a viscosity in the range of 5 to 300 cP, 300 to 3,000 cP, or 3,000 to 30,000 cP. The fluid-like 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-like solution payload may have a viscosity of at most 5 cP, at most 300 cP, at most 3,000 cP, or at most 30,000 cP. The configurations of the multiple cavities 102 and their interconnections 112 can provide a relatively high degree of surface area relative to the volume of payload that retards flow of the fluid-like solution. The interconnections 112 can be sized to restrict flow between cavities 102. For examples, the interconnections 112 can have a smaller diameter than the cavities 102 that they connect. In some embodiments, the interconnected network of cavities is capable of retaining fluid solutions.

[0045] As noted above, at least some of the cavities 102 can be located entirely beneath a surface 108 of the body 104. For example, with respect to FIG. IB, there are three cavities 102-A, 102- B, and 102-C aligned at a longitudinal position that are located entirely beneath the surface 108. As illustrated, the network of cavities 102 can extend through the thickness of the body 104. At least some of the cavities 102 can be located centrally in the body 104 such that they are intersected by the longitudinal axis 101 of the tissue penetrator 100. The cavities 102 can be any size and shape. For examples, the cavities 102 can be spherical, tubular, cube-shaped, irregularly shaped, oblong, etc. The number and/or sizes of the cavities 102 can be selected based on a desired volume of payload. In some embodiments, the cavities 102 can twist relative to the longitudinal axis 101 of the tissue penetrator 100, which can enable more cavities 102 to be formed into a cylindrical body, such as body 104.

[0046] 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 the one or more APIs loaded in the network of cavities 102 to absorb into surrounding tissue to achieve a desired release profile of the one or more APIs. The openings 110 can be arrayed about the longitudinal axis 101 of the tissue penetrator 100 and/or arrayed in the longitudinal direction of the tissue penetrator 100. The openings 110 can be regularly spaced from each other in the longitudinal direction of the tissue penetrator 100 and/or can be regularly spaced from each other in the circumferential direction.

[0047] As noted 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 for holding less viscous solutions and a smaller number of larger cavities can be selected for holding more viscous solutions or pastes. FIG. 2A and 2B illustrate an example of a tissue penetrator 200 that includes a network of larger cavities 202 (larger relative to cavities 102 of FIG. 1A) connected to one another via interconnections 212. FIG. 2B is a cross-section on a plane that includes the 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 for a higher payload-to-tissue contact surface area, which can result in faster absorption of the one or more APIs. FIG. 3A and 3B illustrate an example of a tissue penetrator 300 that includes a network of yet larger cavities 302. FIG. 3B is a cross-section on a plane that includes the longitudinal axis 301. In the illustrated example, there are two cavities 302 that extend in a helical shape about the longitudinal axis 301. The openings 310 in the surface 308 of the body 304 in which the cavities 302 are formed follow the helical shape of the cavities 302. Relative to tissue penetrator 100 of FIG. 1A-C, tissue penetrator 300 may be used for payload substances that are solid or more solid-like than the payload substances used for tissue penetrator 100.

[0048] The tissue penetrators of FIG. 1A-3B include networks of interconnected cavities designed to retain fluid-like payloads in the cavities. FIG. 4A and 4B illustrate an alternative configuration of cavities for retaining fluid-like payloads in a tissue penetrator in which the cavities are not interconnected. The tissue penetrator 400 of FIG. 4A and 4B includes a plurality of noninterconnected cavities 402 formed in the body 404 of the tissue penetrator 400. Openings 410 are formed in the surface 408 of the body 404 that communicate with the cavities 402. The openings 410 are sized smaller than the size of the cavities so that the desired payload does not flow out of the cavities 402 prior to being embedded in the tissue.

[0049] In the illustrated example, the cavities 402 are channel-shaped and have their longitudinal direction extending in the longitudinal direction of the tissue penetrator 400. In other examples, the cavities 402 extend circumferentially about the longitudinal axis 401 of the tissue penetrator 400 or twist 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 ends of the tissue penetrator 400 such that the cavities 402 do not break at their ends through the surface 408 of the tissue penetrator, which further ensures that payload does not prematurely flow out of the cavities 402.

[0050] The openings 410 can extend in a longitudinal direction as illustrated and can extend the full length of the cavities 402 or only a portion of the length of the cavities 402. The opening 410 for each cavity 402 can be continuous as illustrated or there can be a plurality of discrete openings for each cavity 402. The width of the openings 410 is smaller than the width of the cavities 402 (the maximum size of the cavity in a direction orthogonal to the direction of 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, from the perspective of viewing radially outwardly from the cavity 102, the cavity 102 is beneath and partially covered by, for example, a wall 420 of the body 404. The width of the openings 410 can be selected based on the properties of the desired payload such that, for example, the surface tension and viscosity of the payload prevents the payload from flowing out through the openings 410.

[0051] The number, size, and shape of the cavities 402 can be selected based on the desired payload capacity, the characteristics of the payload, and/or the size of the tissue penetrator 400. In the illustrated example, the cavities 402 are evenly arrayed about the longitudinal axis 401, but it should be understood that any arrangement of cavities 402 can be used to meet the requirements of the desired application. The cavities 402 can be isolated from one another, as shown in FIG. 4A and 4B, or can include interconnections with one another beneath the outer surface 408 of the body 404. In some embodiments, the cavities 402 are microfluidic channels.

[0052] In some embodiments, a tissue penetrator may include multiple different cavity configurations, such as to accommodate different types of payloads. For example, a tissue penetrator may have a network of smaller cavities for loading with a first payload that has a lower viscosity and a network of larger cavities for loading with a second payload that has a higher viscosity. This arrangement can provide for delivery of different APIs, different quantity of APIs, and/or different release rates of APIs with the same tissue penetrator. The different networks of cavities can be located in different sections of the tissue penetrator.

[0053] Tissue penetrators can be sized according to a given application, such as for achieving a desired penetration depth and/or for achieving a desired total payload volume. For example, a plurality of relatively small tissue penetrators, often referred to as microneedles, can be mounted to a patch and pressed into the skin for API delivery into the skin, such as beneath the stratum corneum, relatively larger tissue penetrators can be built into oral delivery devices for embedding into the stomach lining, and still large tissue penetrators can be configured for orthopedic application in which the tissue penetrators embed into bone. Tissue penetrators can have a range of different diameters. For example, tissue penetrators can have diameters that correspond with diameters of standard hypodermic needle gauges. For example, a tissue penetrator can have a diameter corresponding to 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, corresponding to an outside diameter of about 4.57 mm, 4.19 mm, 3.76 mm, 3.40 mm, 3.05 mm, 2.77 mm, 2.41 mm, 2.11 mm, 1.83 mm, 1.65 mm, 1.47 mm, 1.27 mm, 1.07 mm, 0.91 mm, 0.82 mm, 0.72 mm, 0.64 mm, 0.57 mm, 0.51 mm, 0.46 mm, 0.41 mm, 0.36 mm, 0.34 mm, 0.31 mm, 0.26 mm, 0.24 mm, 0.21 mm, or 0.18 mm, respectively. Accordingly, tissue penetrators can have an outer diameter of up to 5 mm, such as 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. Tissue penetrator lengths (as measured from a distal end to a 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. Tissue penetrator lengths 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.

[0054] The size of the tissue penetrator and number and size of cavities of the tissue penetrator can be selected to achieve a total cavity volume that provides for a desired total volume of payload. For example, the tissue penetrator can be configured for a total payload volume of at least 0.5 mm³, at least 1 mm³, at least 1.5 mm³, at least 2 mm³, at least 2.5 mm³, at least 3 mm³, at least 3.5 mm³, at least 4 mm³, at least 4.5 mm³, or at least 5 mm³. The tissue penetrator can be configured for a total payload volume of no more than 10 mm³, no more than 8 mm³, no more than 6 mm³, or no more than 4 mm³. [0055] The openings in the outer surface of the tissue penetrators can be configured to provide a total payload-to-tissue contact area (the area of the payload loaded into the cavities that is exposed to the exterior and can come into contact with tissue) desired for a given application, such as to achieve a desired API release profile. Total payload-to-tissue contact area can be at least 1 mm², at least 5 mm², at least 10 mm², at least 15 mm², at least 20 mm², at least 30 mm², or at least 50 mm². Total payload-to-tissue contact area can be at most 100 mm², at most 50 mm², at most 30 mm², at most 20 mm², or at most 10 mm².

[0056] According to various embodiments, tissue penetrators are made using one or more additive manufacturing processes. For example, the network of cavities 102 of tissue penetrator 100 of FIG. 1A-C would not be possible to form using subtractive manufacturing techniques and, thus, are formed using additive manufacturing. FIG. 5 illustrates an example of forming tissue penetrators using additive manufacturing. One or more tissue penetrators 500 (which can include any of tissue penetrator 100, tissue penetrator 200, tissue penetrator 300, and tissue penetrator 400) can be built up on a substrate 550 using a 3D printing system 580. Suitable 3D printing systems can include stereolithography, material jetting systems, binder jet systems, and powder bed fusion systems. The cavities 502 can be formed by the additive manufacturing process, which can allow for the formation of a much greater range of shapes and sizes of cavities than would be achievable or practical using other manufacturing techniques, such as subtractive manufacturing techniques or molding techniques. For example, undercut features, cavities that are interconnected beneath the surface of the tissue penetrator, and/or microfluidic channels are features that may be formed in the tissue penetrators using additive manufacturing that may not be possible using other manufacturing techniques.

[0057] In some embodiments, the payload is formed into the cavities during the additive manufacturing process. FIG. 6 illustrates an example of the 3D printing of a tissue penetrator 600 in which a payload 604 is 3D printed into the cavities 602 simultaneously with the formation of the cavities 602. 3D printing of payloads can allow for different types of payloads to be deposited in different cavities of the same tissue penetrator. For example, payload 604 can be 3D printed into a first set of cavities and a different type of payload 606 can be 3D printed into a second set of cavities 608. [0058] As noted above, various embodiments of tissue penetrators can be incorporated into various drug delivery devices for a variety of different applications. FIG. 7 illustrates an example of an oral delivery device 700 that includes at least one tissue penetrator 702 for delivering one or more APIs to tissue 760 of the digestive tract, such as to the stomach lining. The tissue penetrator 702 can be any of tissue penetrator 100, tissue penetrator 200, tissue penetrator 300, and tissue penetrator 400. The oral delivery device 700 can include a main body 750 to which the tissue penetrator 702 is connected. The main body 750 can be configured for oral administration and to be conveyed by the digestive tract to a desired location where the tissue penetrator is forced into the tissue. In some embodiments, the main body 750 includes a mechanical actuator 752 that forces the tissue penetrator 702 into the tissue — for example, driven by a spring positioned within main body 750. In some embodiments, the tissue penetrator 702 is stored within the main body 750 and deployed at a desired time or upon reaching a desired location. For example, the main 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. The tissue penetrator 702 may be configured to passively fall out of the tissue after a period of time or may be configured to dissolve over a period of time.

[0059] FIG. 8 illustrates an example of a microneedle device 800 that includes a plurality of tissue penetrators 802 that extend from a substrate 850 for embedding into tissue 860. Tissue penetrators 802 can be one or more of tissue penetrator 100, tissue penetrator 200, tissue penetrator 300, and tissue penetrator 400. The microneedle device 800 can be, for example, a patch, an orthoplate, or a hydrogel. The device 800 can be, for example, a patch that is pressed onto a patient’s skin to deliver one or more API’s loaded in the plurality of tissue penetrators beneath the skin surface. The patch can be manually removed after a sufficient period of time has passed for the one or more APIs to be absorbed into the tissue.

[0060] The tissue penetrator could be incorporated into a surgical staple, such as incorporated into or forming the penetrating ends of the surgical staple. The tissue penetrator could be configured to carry an API designed to enhance wound closure and healing. The tissue penetrator may be loaded to a device (e.g., a handheld device) that forces the tissue penetrator into tissue, such as via spring action. For example, a user may position a delivery end of the device at a desired location on a patient and may actuate the device (such as via a button push or trigger pull) and the device may force the tissue penetrator into the tissue to a desired depth.

[0061] The tissue penetrator could be (or could be incorporated into) an implantable rod for oncology treatment. The tissue penetrator could be (or could be incorporated into) orthopedic screws, femoral nails, and/or tendon anchors.

[0062] In some embodiments, tissue penetrator can be made of (or include) a metal, a ceramic material, or a polymeric material. The tissue penetrator material can be (or include) silicon or a metal or metal alloy such as stainless steel, titanium, magnesium allows, or a nickel titanium alloy. Exemplary types of medical grade polymeric materials include polycarbonate, liquid crystalline polymer (LCP), polyether ether ketone (PEEK), cyclic olefin copolymer (COC), and polybutylene terephthalate (PBT).

[0063] In some embodiments, the tissue penetrator material can be (or include) a biodegradable polymeric material. Exemplary types of medical grade biodegradable materials include polylactic acid (PLA), polyglycolic acid (PGA), PGA and PLA copolymer, and polyester-amide polymer (PEA).

[0064] In some embodiments, the tissue penetrator material can be (or include) an absorbable polyurethane, polycaprolactone (PCL), polydioxanone (PDO), polypropylene fumarate (PPF), poly(trimethylene carbonate) (PTMC), combinations thereof, and copolymers thereof with PLA and/or PGA.

[0065] In some embodiments, the tissue penetrator material can be (or include) photocurable resins composed of (meth)acrylate terminated absorbable polyester oligomers.

[0066] In some embodiments, the tissue penetrator or a portion thereof can be made from a dissolvable or degradable material. A dissolvable or degradable material can be any solid material that dissolves or degrades during use. For example, a tissue penetrator may be made to dissolve or degrade sufficiently in the tissue into which it is embedded. In some embodiments, the dissolvable or degradable material is selected from a carbohydrate or a sugar. In some embodiments, the dissolvable or degradable material is polyvinyl pyrrolidone (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.

[0067] Although tissue penetrating devices are described above for delivering an API into tissue, tissue penetrating devices can be configured with a plurality of cavities, according to the principles described herein, for taking samples from tissue. For example, a tissue penetrating device with unfilled cavities can insert into tissue, and cells, fluid, and/or other substance present in the tissue may migrate into the cavities. The tissue penetrating device can then be extracted from the tissue and the sample used, such as for diagnostic purposes.

[0068] In some embodiments, the tissue penetrator or a portion thereof may include an imaging agent for enabling visualization of the tissue penetrator by an imaging system, which can be useful for confirming placement of the tissue penetrator in applications in which the tissue penetrator penetrates tissue within the body. The imaging agent can be, for example, a contrast agent that can be detecting by a fluoroscopic imaging system. In some embodiments, the imaging agent is a component of a material that forms at least a portion of the body 104 of tissue penetrator 100 of FIG. 1A. For example, the imaging agent may be a component of a 3D printing material used to 3D print the tissue penetrator. Additionally, or alternatively, the imaging agent can be loaded into one or more cavities of the tissue penetrator. For example, the imaging agent can be loaded into a set of one or more cavities and payload with one or more APIs can be loaded into a different set of one or more cavities, which can be done using a 3D printing process.

[0069] The foregoing description, for the purpose of explanation, has been described with reference to specific embodiments. However, the illustrative discussions above are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations are possible in view of the above teachings. The embodiments were chosen and described in order to best explain the principles of the techniques and their practical applications. Others skilled in the art are thereby enabled to best utilize the techniques and various embodiments with various modifications as are suited to the particular use contemplated.

[0070] Although the disclosure and examples have been fully described with reference to the accompanying figures, it is to 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 disclosure and examples as defined by the claims. Finally, the entire disclosure of the patents and publications referred to in this application are hereby incorporated herein by reference.

Claims

1. A drug delivery device comprising: at least one tissue penetrating member configured to embed into tissue, the at least one tissue penetrating member comprising: at least one cavity formed beneath an outer surface of the at least one tissue penetrating member, the at least one cavity having a depth from the outer surface and a width in a direction that is orthogonal to a direction of the depth from the outer surface, and at least one opening in the outer surface that communicates with the at least one cavity so that at least one API loaded into the at least one cavity can be absorbed from the at least one cavity into the tissue, wherein a width of the at least one opening is less 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 and at least some of the cavities interconnect beneath the outer surface.

3. The drug delivery device of claim 1 or claim 2, wherein the at least one cavity comprises at least one channel and the at least one opening comprises a slot that extends longitudinally in a longitudinal direction of the at least one channel.

4. The drug delivery device of any of the preceding claims, wherein the at least one cavity comprises a plurality of cavities that are arrayed around a longitudinal axis of the at least one tissue penetrating member.

5. The drug delivery device of any of the preceding claims, wherein the drug delivery device comprises a payload loaded into 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 a surface tension and a viscosity of the payload is such that the payload remains in the at least one cavity prior to the at least one tissue penetrating member embedding into the tissue.

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

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

9. The drug delivery device of any of the preceding claims, wherein the at least one tissue penetrating member comprises a pointed tip for piercing the tissue.

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

11. The drug delivery device of any of the preceding claims, wherein the at least one tissue penetrating 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 of the preceding claims, wherein the at least one tissue penetrating member is 3D printed.

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

14. The drug delivery device of any of the preceding claims, wherein the tissue is a stomach wall.

15. The drug delivery device of any of the preceding claims, wherein the drug delivery device is configured for oral administration.

16. A method of delivering a drug to tissue, the method comprising: embedding at least one tissue penetrating member of a drug delivery device into the tissue, the at least one tissue penetrating member comprising at least one cavity formed beneath an outer surface of the at least one tissue penetrating member, the at least one cavity having a depth from the outer surface and a width in a direction that is orthogonal to a direction of the depth from the outer surface, and at least one opening in the outer surface that communicates with the at least one cavity so that at least one API loaded into the at least one cavity can be absorbed from the at least one cavity into the tissue, wherein a width of the at least one opening is less than the width of the at least one cavity.

17. The method of claim 16, wherein the drug delivery device comprises the drug delivery device of any of claims 2-15.

18. A drug delivery device comprising: at least one tissue penetrating member configured to embed into tissue, the at least one tissue penetrating member comprising: a plurality of cavities that interconnect beneath an outer surface of the at least one tissue penetrating member, and a plurality of openings in the outer surface that communicate with the plurality of cavities so that at least one API loaded into the plurality of cavities can be absorbed from the plurality of cavities into the tissue.

19. The drug delivery device of claim 18, wherein the openings are arrayed about a longitudinal axis of the at least one tissue penetrating member.

20. The drug delivery device of claim 18 or claim 19, wherein the openings are arrayed in a longitudinal direction of the at least one tissue penetrating member.

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

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

23. The drug delivery device of claim 22, wherein at least one of a surface tension and a viscosity of the payload is such that the payload remains in the plurality of cavities prior to the at least one tissue penetrating member embedding into the tissue.

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

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

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

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

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

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

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

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

32. A method of delivering a drug to tissue, the method comprising: embedding at least one tissue penetrating member of a drug delivery device into the tissue, the at least one tissue penetrating member comprising a plurality of cavities that interconnect beneath an outer surface of the at least one tissue penetrating member, and a plurality of openings in the outer surface that communicate with the plurality of cavities so that at least one API loaded into 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 the drug delivery device of any of claims 19-31.