Devices and methods for delivery of drugs via API loaded tissue penetrators

Abstract

A drug delivery device comprises at least one tissue penetrating member configured to be embedded in tissue, the at least one tissue penetrating member comprising: at least one lumen formed below an outer surface of the at least one tissue penetrating member, the at least one cavity has a depth from the outer surface and a width in a direction orthogonal to a direction of the depth from the outer surface; and at least one opening in the outer surface, the at least one opening in communication with the at least one lumen such that at least one API loaded into the at least one lumen can be absorbed from the at least one lumen into the tissue, where the width of the at least one opening is less than the width of the at least one lumen.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 483,241, filed February 3, 2023, which is hereby incorporated by reference in its entirety. Technical Field

[0003] 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 Art

[0004] Microneedles and other tissue penetrating devices are traditionally manufactured as a monolithic structure, where any modification to the design depends on secondary machining (e.g., lathing, laser cutting, water jetting, etc.) to create features in the monolithic structure. These features can be used to carry specific drug payloads or provide sampling ports for fluid diagnostic devices. These features are typically recessed from the monolithic structure because secondary machining is subtractive in nature. In addition, the features that can be manufactured before secondary machining are limited by current tissue penetrating device manufacturing methods. Typical manufacturing methods include molding (e.g., cast molding, injection molding, lost wax molding, etc.), lathing and / or extrusion. Each of these methods limits the ability to have undercut features, negative draft angle structures, and internal channels.

[0005] Based on conventionally used manufacturing techniques, the flexibility of loading drug payloads is limited by the balance of cavity feature size and / or mechanical properties with the properties of the active pharmaceutical ingredient (API) (i.e., maintaining tissue penetration strength with a needle composed of an excipient and drug blend). Given the cavity feature size, there is typically a minimum contact area between the drug payload and the needle device. The effects of the excipient on both adhesion and toughness of the needle limit the options and drug loading capacity (i.e., increasing the excipient to drug ratio). Summary of the Invention

[0006] The drug delivery device includes at least one tissue penetrator that can be loaded with one or more APIs for delivering one or more APIs to the tissue when the tissue penetrator is embedded in the tissue. The tissue penetrator has multiple cavities for loading a payload comprising one or more APIs. The payload can be a fluid solution, and the cavity can be configured to hold the fluid solution so that the fluid solution does not flow out of the cavity before the tissue penetrator is embedded in the tissue. For example, the size of the opening through which the payload leaves the cavity and reaches the surrounding tissue can be configured based on the surface tension and viscosity of the fluid solution so that the fluid solution remains in the cavity. The cavities can be interconnected below the surface of the tissue penetrator to increase the volume of the payload loading capacity while retaining the ability to hold the fluid solution.

[0007] According to one aspect, a drug delivery device includes at least one tissue penetrating member configured to be embedded in tissue, the at least one tissue penetrating member comprising: at least one cavity formed below 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 orthogonal to the direction of the depth from the outer surface; and at least one opening in the outer surface, the at least one opening communicating 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 the width of the at least one opening is smaller than the width of the at least one cavity.

[0008] The at least one cavity may include a plurality of cavities, and at least some of the cavities are interconnected below the outer surface.

[0009] The at least one cavity may include at least one channel, and the at least one opening may include a slot extending longitudinally in a longitudinal direction of the at least one channel.

[0010] The at least one lumen may include a plurality of lumens arranged about the longitudinal axis of the at least one tissue penetrating member.

[0011] The drug delivery device may include a payload loaded into at least one cavity, the payload comprising at least one API. Optionally, at least one of surface tension and viscosity of the payload is such that the payload is retained in the at least one cavity before the at least one tissue-penetrating member is embedded in 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.

[0012] At least one tissue penetrating member may include a pointed tip for penetrating tissue.

[0013] At least one tissue penetrating member may have an outer diameter of at most 2 mm.

[0014] The at least one tissue penetrating member may comprise a plurality of microfluidic channels for retaining at least a portion of the at least one API.

[0015] At least one tissue penetrating member may be 3D printed, such as using stereolithography or material jetting.

[0016] The at least one tissue penetrating member may be configured to embed into the stomach wall.The drug delivery device may be configured for oral administration.

[0017] According to one aspect, a method for delivering a drug to tissue includes embedding at least one tissue penetrating member of a drug delivery device into tissue, the at least one tissue penetrating member comprising: at least one cavity formed below 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 orthogonal to the direction of the depth from the outer surface; and at least one opening in the outer surface, the at least one opening communicating 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 the width of the at least one opening is less than the width of the at least one cavity.

[0018] In the method, the drug delivery device may comprise any of the drug delivery devices described above.

[0019] According to one aspect, a drug delivery device includes at least one tissue penetrating member configured to be embedded in tissue, the at least one tissue penetrating member including a plurality of cavities interconnected below an outer surface of the at least one tissue penetrating member, and a plurality of openings in the outer surface, the plurality of openings communicating with the plurality of cavities so that at least one API loaded into the plurality of cavities can be absorbed into the tissue from the plurality of cavities.

[0020] The openings may be arranged around a longitudinal axis of the at least one tissue penetrating member. The openings may be arranged in a longitudinal direction of the at least one tissue penetrating member.

[0021] Optionally, the longitudinal axis of the at least one tissue penetrating member intersects at least one lumen of the plurality of lumens.

[0022] The drug delivery device may include at least one payload comprising at least one API. Optionally, at least one of surface tension and viscosity of the payload is such that the payload is retained within the plurality of cavities prior to embedding of the at least one tissue-penetrating member 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.

[0023] At least one tissue penetrating member may include a pointed tip for penetrating tissue.

[0024] At least one tissue penetrating member may have an outer diameter of at most 2 mm.

[0025] At least one tissue penetrating member may be 3D printed, such as using stereolithography or material jetting.

[0026] The at least one tissue penetrating member may be configured to embed into the stomach wall.The drug delivery device may be configured for oral administration.

[0027] According to one aspect, a method of delivering a drug to tissue includes embedding at least one tissue penetrating member of a drug delivery device into tissue, the at least one tissue penetrating member comprising a plurality of cavities interconnected beneath an outer surface of the at least one tissue penetrating member, and a plurality of openings in the outer surface, the plurality of openings communicating 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.

[0028] In the method, the drug delivery device may comprise any of the drug delivery devices described above. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0030] Figures 1A to 1C An exemplary tissue penetrator comprising a network of interconnected lumens for loading with one or more APIs is shown;

[0031] Figure 2A and Figure 2B Shows a ratio Figures 1A to 1C Examples of tissue penetrators with larger lumens;

[0032] Figure 3A and Figure 3B Shows a ratio Figures 1A to 1C as well as Figure 2A and Figure 2B Examples of tissue penetrators with larger lumens;

[0033] Figure 4A and Figure 4B An example of a tissue penetrator with an unattached lumen is shown;

[0034] Figure 5 An example of 3D printing of one or more tissue penetrators is shown;

[0035] Figure 6 An example of 3D printing of a tissue penetrator is shown, wherein a payload is 3D printed into a lumen of the tissue penetrator;

[0036] Figure 7 An example of an oral delivery device comprising at least one tissue penetrator is shown; and

[0037] Figure 8 An example of a microneedle device comprising a plurality of tissue penetrators extending from a base is shown. DETAILED DESCRIPTION

[0038] Described herein is a drug delivery device comprising a tissue penetrator that can be embedded in tissue to deliver one or more APIs to the tissue. The tissue penetrator can include multiple cavities that can be loaded with a payload comprising one or more APIs that are absorbed into the tissue when the tissue penetrator is embedded in the tissue. The payload can be a fluid solution (e.g., a low modulus gel, a viscous solution, etc.), and the cavity can be configured to maintain a fluid solution so that the fluid solution does not flow out of the cavity before use.

[0039] An opening can be formed in the outer surface of the tissue penetrator that communicates with the cavity so that when the tissue penetrator is embedded in the tissue, the payload loaded in the cavity can migrate into the surrounding tissue. The size of the opening can be configured based on the characteristics of the fluid-like payload so that the fluid-like payload cannot flow out through the opening prematurely. The cavity can extend below the outer surface of the tissue penetrator so that, for example, the width of the opening is greater than the corresponding width of the cavity it is connected to. 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 to retain the fluid-like solution in the cavity. The tissue penetrator can be made via additive manufacturing, which can achieve cavity configurations that cannot be achieved via subtractive manufacturing techniques.

[0040] Reference will now be made in detail to embodiments and implementations of 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 various aspects of the devices, systems, and methods described herein combined in any suitable manner, with combinations of all or some of the described aspects.

[0041] In the following description, it should be understood that, unless the context clearly indicates otherwise, the singular forms "a", "an", and "the" used in the following description are intended to include the plural forms as well. It should also be understood that, as used herein, the term "and / or" refers to and encompasses any and all possible combinations of one or more of the associated listed items. It should also be understood that, when used herein, the terms "include" and / or "comprising" specify the presence of stated features, integers, steps, operations, elements, parts, and / or units, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, parts, units, and / or groups thereof.

[0042] Figures 1A to 1C An exemplary tissue penetrator 100 is shown that includes a plurality of lumens 102 for loading with one or more payloads including one or more APIs. Figure 1B is a cross-section of the tissue penetrator 100 on a plane aligned with the longitudinal axis 101 of the tissue penetrator 100, and Figure 1C 101 is a cross-section taken on a plane perpendicular to the longitudinal axis 101. The tissue penetrator 100 is configured to penetrate the surface of tissue and embed into the tissue. When embedded in the tissue, the API loaded in the cavity 102 is absorbed into the surrounding tissue.

[0043] Tissue penetrator 100 comprises a main body 104, in which a network of chambers 102 is formed. Top 106 can be configured to penetrate into tissue, such as penetrate into skin or gastric mucosa. As shown, top 106 can be conical in shape, or can include one or more bevels forming a sharp tip. Main body 104 can be straight as shown, or can be curved or otherwise angled. Main body 104 can have one or more barbs or other prominent features that help to keep tissue penetrator in tissue. The proximal end 116 of main body 104 can be attached to or be configured to be attached to the main body (not shown) of a drug delivery device, such as an intra-organ drug delivery device or an orthopedic implant. Multiple tissue penetrators 100 can be mounted to substrates, such as transdermal patches or surgical meshes, for delivering one or more APIs simultaneously at multiple locations.

[0044] A network of cavities 102 is formed in 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, such as Figures 1A to 1C The payload may be loaded into the cavity 102 for delivery to the tissue. The payload may include one or more APIs and optional excipients. At least some of the cavities 102 are completely below the surface 108 of the body 104, such as Figure 1B The body 104 includes cavities 102-A, 102-B, and 102-C. The cavities 102 can be interconnected with each other via interconnects 112, thereby 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 be absorbed into the surrounding tissue through these openings 110.

[0045] The configuration of the interconnected network of cavities 102 and the configuration of openings 110 can enable substances having fluid-like properties (e.g., fluid-like properties at room temperature) to be retained in cavities 102. Examples of such fluid-like substances include low modulus gels, viscous solutions, semi-fluids, semi-solids, quasi-solids, pastes, and the like. The openings 110 can be sized based on the range of viscosities and / or surface tensions of the desired fluid-like solution payload to be loaded into the cavity 102 so that the fluid-like solution is restricted from flowing out through the openings 110 unless absorbed into the surrounding tissue. The fluid-like solution payload can have a viscosity in the range of 5 cP to 300 cP, 300 cP to 3,000 cP, or 3,000 cP to 30,000 cP. The fluid-like solution payload can have a viscosity of at least 5 cP, at least 300 cP, at least 3,000 cP, or at least 30,000 cP. The fluidic 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 configuration of the plurality of cavities 102 and their interconnects 112 may provide a relatively high degree of surface area relative to the volume of the payload, which hinders the flow of the fluidic solution. The dimensions of the interconnects 112 may be designed to restrict flow between the cavities 102. For example, the interconnects 112 may have a smaller diameter than the cavities 102 to which they connect. In some embodiments, the network of interconnected cavities is capable of retaining a fluidic solution.

[0046] As described above, at least some of the cavities 102 may be located completely below the surface 108 of the body 104. For example, relative to Figure 1B , there are three cavities 102-A, 102-B, and 102-C aligned at longitudinal positions, which are completely below surface 108. As shown, the network of cavities 102 can extend through the thickness of body 104. At least some of the cavities 102 can be located in the center of body 104 so that they intersect the longitudinal axis 101 of tissue penetrator 100. Cavities 102 can have any size and shape. For example, cavity 102 can be spherical, tubular, cubic, irregular, elliptical, etc. The number and / or size of cavities 102 can be selected based on the desired volume of the payload. In some embodiments, cavity 102 can be twisted relative to the longitudinal axis 101 of tissue penetrator 100, which can enable more cavities 102 to be formed into a cylindrical body, such as body 104.

[0047] Any number of openings 110 may be formed in the surface 108 of the body 104. The number and / or size of the openings 110 may be selected to provide a desired amount of exposed surface area for the one or more APIs loaded into the network of cavities 102 to be absorbed into the surrounding tissue, thereby achieving a desired release profile for the one or more APIs. The openings 110 may be arranged about the longitudinal axis 101 of the tissue penetrator 100 and / or in the longitudinal direction of the tissue penetrator 100. The openings 110 may be regularly spaced apart from one another in the longitudinal direction of the tissue penetrator 100 and / or may be regularly spaced apart from one another in the circumferential direction.

[0048] As described above, the tissue penetrator 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 lower viscosity solutions, and a smaller number of larger cavities can be selected for holding higher viscosity solutions or pastes. Figure 2A and Figure 2B An example of a tissue penetrator 200 is shown that includes larger lumens 202 (relative to the Figure 1A The cavity 102 is larger). Figure 2B 201. Relative to tissue penetrator 100, tissue penetrator 200 includes larger openings 210 communicating with the network of lumens 202. These larger openings 210 provide a higher surface area for payload to contact tissue, which can result in faster absorption of one or more APIs. Figure 3A and Figure 3B An example of a tissue penetrator 300 comprising a network of larger lumens 302 is shown. Figure 3B is a cross section on a plane including the longitudinal axis 301. In the example shown, there are two cavities 302 extending in a spiral shape around the longitudinal axis 301. The openings 310 in the surface 308 of the body 304 forming the cavities 302 follow the spiral shape of the cavities 302. Figures 1A to 1C As with tissue penetrator 100 , tissue penetrator 300 may be used with a payload material that is solid or more solid than the payload material used for tissue penetrator 100 .

[0049] Figures 1A to 3B The tissue penetrator comprises a network of interconnected lumens designed to retain a fluid payload within the lumens. Figure 4A and Figure 4B An alternative configuration of lumens for retaining a fluid payload in a tissue penetrator is shown, wherein the lumens are not interconnected. Figure 4A and Figure 4BThe tissue penetrator 400 includes a plurality of non-interconnected cavities 402 formed in a 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 cavities so that a desired payload does not flow out of the cavities 402 before being embedded in tissue.

[0050] In the example shown, lumen 402 is channel-shaped and its longitudinal direction extends in the longitudinal direction of tissue penetrator 400. In other examples, lumen 402 extends circumferentially about longitudinal axis 401 of tissue penetrator 400 or twists relative to longitudinal axis 401 of tissue penetrator 400. Lumen 402 can extend along a portion of tissue penetrator 400 and can stop short of reaching the end of tissue penetrator 400 so that lumen 402 does not rupture at its end through surface 408 of the tissue penetrator, further ensuring that the payload does not prematurely exit lumen 402.

[0051] The opening 410 may extend in the longitudinal direction as shown and may extend the entire length of the cavity 402 or only a portion of the length of the cavity 402. The opening 410 of each cavity 402 may be continuous, as shown, or there may be multiple discrete openings for each cavity 402. The width of the opening 410 is less than the width of the cavity 402 (the maximum dimension of the cavity in a direction perpendicular to the depth of the cavity from the outer surface 408 of the body 404) so ​​that the outer surface 408 of the body 404 extends over a portion of the cavity. In other words, from the perspective of viewing the cavity 102 radially outward, the cavity 102 is located below and partially covered by the wall 420 of the body 404, for example. The width of the opening 410 can be selected based on the characteristics of the desired payload so that, for example, the surface tension and viscosity of the payload prevent the payload from flowing out through the opening 410.

[0052] The number, size, and shape of cavities 402 may be selected based on the desired payload capacity, the characteristics of the payload, and / or the size of tissue penetrator 400. In the example shown, cavities 402 are evenly spaced about longitudinal axis 401, but it will be understood that any arrangement of cavities 402 may be used to meet the requirements of a desired application. Figure 4A and Figure 4B As shown, the cavities 402 can be isolated from one another, or can include interconnections with one another beneath the exterior surface 408 of the body 404. In some embodiments, the cavities 402 are microfluidic channels.

[0053] In some embodiments, a tissue penetrator can include multiple different cavity configurations, such as to accommodate different types of payloads. For example, a 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 can provide for the delivery of different APIs, different amounts of APIs, and / or APIs with different release rates using the same tissue penetrator. Different cavity networks can be located in different parts of the tissue penetrator.

[0054] The tissue penetrator 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 (commonly referred to as microneedles) can be mounted on a patch and pressed into the skin for delivering the API to the skin, such as below the stratum corneum, a relatively large tissue penetrator can be built into an oral delivery device for embedding into the gastric mucosa, and an even larger tissue penetrator can be constructed for orthopedic applications where the tissue penetrator is embedded into the bone. The tissue penetrator can have a range of different diameters. For example, the tissue penetrator can have a diameter corresponding to the diameter of a standard hypodermic needle. For example, the tissue penetrator can have a diameter corresponding to hypodermic needle gauge 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 approximately 4.57 mm, 4.19 mm, 3.76 mm, 3.40 mm, 3.05 mm, 2.77 mm, 2. 1 mm, 0.41 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. Thus, the tissue penetrator can have an outer diameter of at most 5 mm, such as at most 4.5 mm, at most 4 mm, at most 3.5 mm, at most 3 mm, at most 2.5 mm, at most 2 mm, at most 1.5 mm, at most 1 mm, or at most 0.5 mm. The tissue penetrator length (as measured from the distal end to the proximal end attached or attachable to the 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 tissue penetrator length 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.

[0055] The size of the tissue penetrator and the number and size of the lumens of the tissue penetrator can be selected to achieve a total lumen volume that provides a desired total volume of payload. For example, the tissue penetrator can be configured for at least 0.5 mm 3 , at least 1mm 3 , at least 1.5mm 3 , at least 2mm 3 , at least 2.5mm 3 , at least 3mm 3 , at least 3.5mm 3 , at least 4mm 3 , at least 4.5mm 3 or at least 5mm 3 Total payload volume. Tissue penetrators can be constructed for no more than 10 mm 3 , not more than 8mm 3 , not more than 6mm 3 or no more than 4mm 3 Total payload volume.

[0056] The openings in the outer surface of the tissue penetrator can be configured to provide the total payload to tissue contact area (the area of ​​the payload loaded into the cavity that is exposed to the outside and can contact the tissue) required for a given application, such as to achieve a desired API release profile. The total payload to tissue contact area can be at least 1 mm 2 , at least 5mm 2 , at least 10mm 2 , at least 15mm 2 , at least 20mm 2 , at least 30mm 2 or at least 50mm 2 The total payload and tissue contact area can be up to 100mm 2 , up to 50mm 2 , up to 30mm 2 , up to 20mm 2 or up to 10mm 2 .

[0057] According to various embodiments, the tissue penetrator is made using one or more additive manufacturing processes. For example, Figures 1A to 1C The network of lumens 102 of tissue penetrator 100 would not be possible to form using subtractive manufacturing techniques, and is therefore formed using additive manufacturing. Figure 5An example of a tissue penetrator formed using additive manufacturing is shown. One or more tissue penetrators 500 (which may include any of tissue penetrator 100, tissue penetrator 200, tissue penetrator 300, and tissue penetrator 400) can be constructed on a substrate 550 using a 3D printing system 580. Suitable 3D printing systems may include stereolithography, material jetting systems, binder jetting systems, and powder bed fusion systems. Cavity 502 can be formed using an additive manufacturing process that allows for the formation of cavities of a wider range of shapes and sizes than is achievable or practical using other manufacturing techniques (such as subtractive manufacturing techniques 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 a tissue penetrator using additive manufacturing that may not be possible using other manufacturing techniques.

[0058] In some embodiments, the payload is formed into the cavity during the additive manufacturing process. Figure 6 An example of 3D printing of a tissue penetrator 600 is shown, wherein a payload 604 is 3D printed into the cavity 602 simultaneously with the formation of the cavity 602. 3D printing of payloads can allow 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.

[0059] As described above, various embodiments of tissue penetrators may be incorporated into various drug delivery devices for a variety of different applications. Figure 7An example of an oral delivery device 700 is shown that includes at least one tissue penetrator 702 for delivering one or more APIs to tissue 760 of the digestive tract, such as the gastric mucosa. Tissue penetrator 702 can be any of tissue penetrator 100, tissue penetrator 200, tissue penetrator 300, and tissue penetrator 400. Oral delivery device 700 can include a main body 750 to which tissue penetrator 702 is attached. Main body 750 can be configured for oral administration and delivered through the digestive tract to a desired location in the tissue where the tissue penetrator is forced into the tissue. In some embodiments, main body 750 includes a mechanical actuator 752 that forces tissue penetrator 702 into the tissue, for example, driven by a spring positioned within main body 750. In some embodiments, tissue penetrator 702 is stored within 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 trap 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.

[0060] Figure 8 An example of a microneedle device 800 is shown, which includes a plurality of tissue penetrators 802 extending from a substrate 850 to be embedded in tissue 860. Tissue penetrators 802 can be one or more of tissue penetrators 100, 200, 300, and 400. Microneedle device 800 can be, for example, a patch, an orthopedic plate, or a hydrogel. Device 800 can be, for example, a patch that is pressed against a patient's skin to deliver one or more APIs loaded into the plurality of tissue penetrators below the skin surface. After sufficient time has passed for the one or more APIs to be absorbed into the tissue, the patch can be manually removed.

[0061] The tissue penetrator can be incorporated into a surgical staple, such as being incorporated into or forming the penetrating end of a surgical staple. The tissue penetrator can be configured to carry an API designed to enhance wound closure and healing. The tissue penetrator can be loaded onto a device (e.g., a handheld device) that forces the tissue penetrator into tissue, such as via a spring action. For example, a user can position the delivery end of the device at a desired location on the patient, and can actuate the device (e.g., via a button push or trigger pull), and the device can force the tissue penetrator into the tissue to a desired depth.

[0062] The tissue penetrator may be an implantable rod for tumor treatment (or may be incorporated therein). The tissue penetrator may be an orthopedic screw, a femoral nail, and / or a tendon anchor (or may be incorporated therein).

[0063] In some embodiments, the tissue penetrator can be made of (or include) a metal, a ceramic material, or a polymer material. The tissue penetrator material can be (or include) silicon or a metal or metal alloy, such as stainless steel, titanium, a magnesium alloy, or a nickel-titanium alloy. Exemplary types of medical-grade polymer materials include polycarbonate, liquid crystal polymer (LCP), polyetheretherketone (PEEK), cyclic olefin copolymer (COC), and polybutylene terephthalate (PBT).

[0064] In some embodiments, the tissue penetrator material can be (or include) a biodegradable polymer material. Exemplary types of medical-grade biodegradable materials include polylactic acid (PLA), polyglycolic acid (PGA), copolymers of PGA and PLA, and polyester-amide polymers (PEA).

[0065] In some embodiments, the tissue penetrator material can be (or include) absorbable polyurethane, polycaprolactone (PCL), polydioxanone (PDO), polypropylene fumarate (PPF), poly(trimethylene carbonate) (PTMC), combinations thereof, and copolymers thereof with PLA and / or PGA.

[0066] In some embodiments, the tissue penetrator material can be (or include) a photocurable resin composed of a (meth)acrylate-terminated absorbable polyester oligomer.

[0067] In some embodiments, the tissue penetrator or a portion thereof can be made of a soluble or degradable material. The soluble or degradable material can be any solid material that dissolves or degrades during use. For example, the tissue penetrator can be made to fully dissolve or degrade in the tissue in which it is embedded. In some embodiments, the soluble or degradable material is selected from a carbohydrate or sugar. In some embodiments, the soluble or degradable material is polyvinyl pyrrolidone (PVP). In some embodiments, the soluble or degradable material is selected from the group consisting of: hyaluronic acid, carboxymethyl cellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, sucrose, glucose, dextran, trehalose, maltodextrin, and any combination thereof.

[0068] Although a tissue penetrating device for delivering an API into tissue is described above, according to the principles described herein, a tissue penetrating device can be configured with multiple cavities for obtaining samples from tissue. For example, a tissue penetrating device with an unfilled cavity can be inserted into tissue, and cells, fluids, and / or other substances present in the tissue can migrate into the cavity. The tissue penetrating device can then be extracted from the tissue and the sample used, such as for diagnostic purposes.

[0069] 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 is useful for confirming placement of the tissue penetrator in applications where the tissue penetrator penetrates tissue within the body. The imaging agent may be, for example, a contrast agent detectable by a fluorescence imaging system. In some embodiments, the imaging agent is a contrast agent that forms a Figure 1A The imaging agent may be a component of the material of at least a portion of the body 104 of the tissue penetrator 100. For example, the imaging agent may be a component of the 3D printing material used to 3D print the tissue penetrator. Additionally or alternatively, the imaging agent may be loaded into one or more cavities of the tissue penetrator. For example, the imaging agent may be loaded into one or more cavities, and a payload having one or more APIs may be loaded into a different group of one or more cavities, which may be accomplished using a 3D printing process.

[0070] For purposes of explanation, the foregoing description has been described with reference to specific embodiments. However, the foregoing illustrative discussions are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations of the present disclosure are possible in light of the foregoing teachings. The embodiments have been selected and described in order to best explain the principles of these techniques and their practical applications. Thus, others skilled in the art will be able to best utilize these techniques and various embodiments with various modifications suitable for the specific applications contemplated.

[0071] 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 hereby incorporated by reference.

Claims

1. A drug delivery device comprising: at least one tissue penetrating member configured to be embedded in tissue, the at least one tissue penetrating member comprising: at least one lumen formed below an outer surface of the at least one tissue penetrating member, the at least one lumen having a depth from the outer surface and a width in a direction orthogonal to the direction of the depth from the outer surface, and At least one opening in the outer surface, the at least one opening communicating with the at least one lumen such that at least one API loaded into the at least one lumen can be absorbed from the at least one lumen into the tissue, wherein a width of the at least one opening is smaller than a width of the at least one lumen.

2. The drug delivery device according to claim 1, wherein The at least one cavity comprises a plurality of cavities, and at least some of the cavities are interconnected below the outer surface.

3. The drug delivery device according to 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 extending longitudinally in a longitudinal direction of the at least one channel.

4. A drug delivery device according to any one of the preceding claims, wherein The at least one lumen comprises a plurality of lumens arranged about a longitudinal axis of the at least one tissue penetrating member.

5. A drug delivery device according to any one of the preceding claims, wherein The drug delivery device includes a payload loaded into the at least one cavity, the payload including the at least one API.

6. The drug delivery device according to claim 5, wherein: At least one of surface tension and viscosity of the payload causes the payload to be retained in the at least one cavity prior to embedding of the at least one tissue penetrating member into the tissue.

7. The drug delivery device according to claim 5 or claim 6, wherein: The payload is 3D printed into 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. A drug delivery device according to any one of the preceding claims, wherein: The at least one tissue penetrating member comprises a pointed tip for penetrating the tissue.

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

11. A drug delivery device according to any one of the preceding claims, wherein The at least one tissue penetrating member comprises a plurality of microfluidic channels for retaining at least a portion of the at least one API.

12. A drug delivery device according to any one 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. A drug delivery device according to any one of the preceding claims, wherein: The tissue is the stomach wall.

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

16. A method of delivering a drug to a tissue, the method comprising: At least one tissue penetrating member of a drug delivery device is embedded in the tissue, the at least one tissue penetrating member comprising: at least one cavity formed below 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 orthogonal to the direction of the depth from the outer surface; and at least one opening in the outer surface, the at least one opening being connected to 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 the width of the at least one opening is smaller than the width of the at least one cavity.

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

18. A drug delivery device comprising: at least one tissue penetrating member configured to be embedded in tissue, the at least one tissue penetrating member comprising: a plurality of interconnected lumens beneath an outer surface of the at least one tissue penetrating member, and A plurality of openings are provided in the outer surface, the plurality of openings being in communication with the plurality of cavities to enable at least one API loaded into the plurality of cavities to be absorbed from the plurality of cavities into the tissue.

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

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

21. The drug delivery device according to any one of claims 18 to 20, wherein The longitudinal axis of the at least one tissue penetrating member intersects at least one lumen of the plurality of lumens.

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

23. The drug delivery device of claim 22, wherein: At least one of surface tension and viscosity of the payload causes the payload to be retained within the plurality of cavities prior to embedding of the at least one tissue penetrating member into the tissue.

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

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

27. The drug delivery device according to any one of claims 18 to 26, wherein The at least one tissue penetrating member has an outer diameter of at most 2 mm.

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

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

32. A method of delivering a drug to a tissue, the method comprising: At least one tissue penetrating member of a drug delivery device is embedded in the tissue, the at least one tissue penetrating member comprising a plurality of cavities interconnected below an outer surface of the at least one tissue penetrating member, and a plurality of openings in the outer surface, the plurality of openings communicating with the plurality of cavities to enable at least one API loaded into the plurality of cavities to be absorbed from the plurality of cavities into the tissue.

33. The method according to 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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