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

Abstract

The drug delivery device includes at least one tissue-penetrating member configured to be implanted in tissue, the at least one tissue-penetrating member including a plurality of cavities and at least one payload including at least one active pharmaceutical ingredient (API), the at least one payload being loaded into the plurality of cavities such that the at least one API can be absorbed into the tissue when the at least one tissue-penetrating member is implanted in the tissue, and a ratio of a surface area of ​​the plurality of cavities to a volume of the plurality of cavities is at least 0.5:1.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 483,240, 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 the 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 tissue-penetrating drug delivery device includes multiple cavities that can be loaded with a payload for delivering one or more APIs to tissue. The multiple cavities can be configured to provide a desired release profile for the payload (i.e., excipients and APIs) and / or to increase the drug payload. The multiple cavities can be configured to provide a relatively high payload-to-cavity contact area, which improves payload retention within the cavity and allows a lower percentage of excipients to be used in the payload, thereby increasing the amount of API that can be loaded into the tissue-penetrating device.

[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 a plurality of cavities and at least one payload including at least one active pharmaceutical ingredient (API), the at least one payload being loaded into the plurality of cavities such that the at least one API can be absorbed into the tissue when the at least one tissue-piercing member is implanted in the tissue, and a ratio of a surface area of ​​the plurality of cavities to a volume of the plurality of cavities is at least 0.5:1.

[0007] The plurality of cavities can be arranged around a longitudinal axis of the at least one tissue-piercing member. The at least one payload can include an excipient, and a ratio of the at least one API to the excipient in the payload can be at least 2:1.

[0008] The at least one tissue-piercing member may be 3D printed. The at least one tissue-piercing member may be 3D printed using stereolithography or material jetting. The at least one payload may be 3D printed within the plurality of cavities.

[0009] The at least one tissue-piercing member may include a sharp tip for piercing tissue.

[0010] The at least one tissue-piercing member may have an outer diameter of up to 2 millimeters. The at least one payload may have a total volume of at least 2 cubic millimeters. The at least one payload may have a total tissue-contacting surface area of ​​at least 20 square millimeters.

[0011] The at least one tissue-piercing member may be configured to penetrate into the stomach wall.The drug delivery device may be configured for oral administration.

[0012] 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 payload.

[0013] The drug delivery device may have multiple different APIs loaded into multiple cavities.

[0014] According to one embodiment, a method of delivering at least one API to tissue includes using any of the drug delivery devices described above. For example, the method may include implanting at least one tissue-piercing member into the tissue such that the at least one API can be absorbed into the tissue. [Brief explanation of the drawings]

[0015] 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 multiple cavities for loading one or more APIs. [Figure 1B] 1 illustrates an exemplary tissue penetrator that includes multiple cavities for loading one or more APIs. [Figure 2] 1 is an example of a conventional tissue-piercing member configuration. [Figure 3] 1 shows an example of a tissue penetrator with multiple microfluidic channels. [Figure 4A] 3A-3C are cross-sectional views of a portion of a tissue penetrator 300 showing examples of possible configurations of microfluidic channels. [Figure 4B] 3A-3C are cross-sectional views of a portion of a tissue penetrator 300 showing examples of possible configurations of microfluidic channels. [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

[0016] Described herein are drug delivery devices that include 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 configuration of the multiple cavities can be selected to achieve different release profiles and / or increased drug payloads.

[0017] According to various embodiments, the multiple cavities can be configured to maximize the API-to-excipient ratio in the payload. The multiple cavities can be configured to have a relatively large contact area with the payload loaded into the cavity. This large contact area reduces the burden on excipients to provide adhesion, meaning that a given volume of payload can have a higher API-to-excipient ratio, effectively increasing the API loading capacity of the tissue penetrator.

[0018] 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.

[0019] 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. It should also 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 should be further understood that the terms "includes," "including," "comprises," and / or "comprising," as used herein, indicate 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.

[0020] 1A and 1B show an exemplary tissue penetrator 100 that includes multiple cavities 102 for loading one or more payloads, including one or more APIs. 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 into the surrounding tissue. As explained further below, the configuration of the cavities 102 provides a high payload-to-penetrator contact surface area that better retains the payload within the cavity, requiring fewer excipients and a greater relative proportion of API in the payload.

[0021] The tissue penetrator 100 includes a body 104 having a cavity 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.

[0022] A plurality of cavities 102 are formed in the body 104 and arranged around a longitudinal axis 105 of the tissue penetrator 100. A payload may be loaded into the cavities 102 for delivery to the tissue. The payload may include one or more APIs and, optionally, excipients. In Figures 1A and 1B, one of the cavities, cavity 102-A, is shown loaded with a payload 120.

[0023] The configuration of the cavities 102 can be tailored to the desired payload volume and exposed surface area of ​​the payload, which influence the amount of payload available for absorption into tissue and its rate of absorption. Referring to the cross-sectional view of FIG. 1B , the volume of each cavity 102 is defined by the area 118 of the cavity 102 at the surface 110 of the body 104 (defining the exposed surface area of ​​the payload that can contact tissue when the payload is loaded into the cavity 102), the depth 115 of the cavity 102 from the surface 110 of the body 104, and any draft angle 114 of the walls 112 of the cavity 102. The walls 112 may be straight or may have a positive or negative draft angle. In the illustrated example, the walls 112 have a positive draft angle 114. The depth 115 of the cavity 102 can be less than the radius of the body 104. The depth 115 of the cavities 102 may be selected to provide sufficient volume for the payload while still providing sufficient diameter material thickness 130 of the body 104 between the cavities 102 so that the body 104 has sufficient strength to withstand penetration forces.

[0024] The shape, size, and number of cavities 102 can be tailored for a given application to provide a desired release profile and / or payload volume. The cavity configuration can be adjusted to adjust the payload exposed surface area (the surface area of ​​the payload exposed to the surrounding tissue, as indicated by reference numeral 122 in FIG. 1B) to volume ratio. A higher surface area to volume ratio can provide a faster release rate, as more of the payload is available for contact with the surrounding tissue. A higher surface area to volume ratio can be achieved, for example, by a greater number of shallower cavities.

[0025] Another advantage that may be provided by the cavities 102 of the tissue penetrator 100 is an increased drug-to-excipient ratio compared to conventional tissue penetrating members. An example of a conventional tissue penetrating member configuration is shown in FIG. 2. The conventional tissue penetrating member 200 includes a single large cavity 202 for loading a payload. When comparing the tissue penetrating member 100 to a conventional tissue penetrating member 200, the same cavity volume (and therefore payload volume) may be achieved with a much higher contact surface area between the surface of the cavity 102 and the payload. In other words, the relatively multiple smaller cavities 102 of the tissue penetrator 100 provide more contact area between the payload and the cavity wall 112 than the single large cavity 202 of the conventional tissue penetrating member 200. This greater contact area between the tissue penetrator and the payload leads to a reduced need for excipients to provide adhesive forces to hold the payload to the tissue penetrator 100. As the contact surface area increases, an effective payload exposed surface area (e.g., the exposed surface area of ​​the payload shown by reference numeral 122 in FIG. 1B) equivalent to that of conventional tissue-piercing members 200 can be achieved with a reduced excipient volume fraction. This required relatively lower excipient volume fraction allows for a greater amount of API for the same payload volume compared to conventional tissue-piercing members 200.

[0026] An example of the relatively high payload-to-cavity contact area provided by the tissue penetrator 100 of FIG. 1 relative to the conventional tissue penetrating member 200 of FIG. 2 is 2.5 mm 3 This can be demonstrated by configuring both designs to have the same total cavity volume of approximately 0.13 mm. The contact area between the walls 204 of the cavity 202 of the conventional tissue-piercing member 200 and the payload loaded within the cavity 202 is approximately 0.13 mm. 2 In contrast, the total contact area between the walls 112 and base 113 of the cavity 102 of the tissue penetrator 100 and the payload loaded within the cavity 102 is approximately 11.72 mm 2Thus, tissue penetrator 100 can be configured to provide approximately two orders of magnitude greater payload-to-cavity contact area relative to conventional designs of the same payload volume. In these exemplary comparative configurations, assuming a conventional single-cavity design requires a conventional 1:1 API-to-excipient ratio for retention within the cavity, tissue penetrator 100 can provide the same payload volume with an API-to-excipient ratio of greater than 9:1, meaning that tissue penetrator 100 can be loaded with nine times the amount of API as conventional designs for the same payload volume. This increase in API loading capacity can be achieved without excessively increasing the payload exposed surface area (the surface area of ​​the payload that can come into contact with tissue) and, therefore, without excessively affecting the absorption rate. For example, if a conventional design and tissue penetrator 100 have a 2.5 mm 3 In an example configured for a total cavity volume of approximately 22.45 mm , the payload exposed surface area is approximately 22.45 mm for a conventional tissue penetrating member 200. 2 and is approximately 26.35 mm for the tissue penetrator 100. 2 is.

[0027] Another advantage that may be provided by multiple cavities 102 of tissue penetrator 100 is the ability to load different APIs into the same tissue penetrator. In other words, with reference to FIG. 1B, a first cavity 102-A may be loaded with a payload 120 having a first API or combination of APIs, and a second cavity 102-B may be loaded with a different payload 124 having a second API or combination of APIs that is different from the first.

[0028] 1A and 1B are merely exemplary, and those skilled in the art will appreciate that the cavities can be configured differently for different applications to achieve a desired balance between payload volume, payload exposed surface area, and payload-to-penetrator contact area. The tissue penetrator can be configured to provide a cavity surface area to cavity volume ratio of at least 0.5:1, at least 1:1, at least 1.5:1, at least 2:1, at least 2.5:1, at least 3:1, at least 3.5:1, or at least 4:1.

[0029] Given the relatively high cavity surface area to cavity volume ratio of the penetrators described herein, suitable payloads can be loaded into the penetrators at API to excipient ratios of at least 1:1, at least 2:1, at least 3:1, at least 4:1, at least 5:1, at least 6:1, at least 7:1, at least 8:1, at least 9:1, or at least 10:1. Penetrators can be configured for payloads having API to excipient ratios of up to 100:1, up to 50:1, up to 20:1, up to 15:1, or up to 10:1.

[0030] 1A and 1B are shown as having a hexagonal shape with positive draft sides, it should be understood that this shape is merely exemplary and the cavity may be any shape, such as cylindrical, conical, cubic, slot-shaped, or irregular, and may have straight sides, curved sides, negative draft sides, and any combination thereof. The cavities may be elongated, i.e., their major dimension may extend in the direction of the longitudinal axis 105 of the penetrator 100, or may extend circumferentially around the longitudinal axis 105.

[0031] In some embodiments, the multiple cavities can be or include multiple microfluidic channels. According to various embodiments, the microfluidic channels can be used in concert with an osmotic agent to generate a pressure gradient for delivering a payload to tissue. The microfluidic channels can be used for fluid entry and / or API exit, which can be tailored for each specific payload. Additionally, the microfluidic channels can be used when extended API release times are desired.

[0032] 3 shows an example of a tissue penetrator 300 comprising a plurality of microfluidic channels 302 formed in an array extending longitudinally on a surface of a body 304 of the tissue penetrator 300. It will be understood by those skilled in the art that this configuration of microfluidic channels is merely exemplary, and that any desired arrangement of microfluidic channels may be formed within the body 304.

[0033] 4A and 4B are cross-sectional views of a portion of the tissue penetrator 300 of FIG. 3, illustrating examples of possible configurations of microfluidic channels, such as the microfluidic channel 302 of FIG. 3. The microfluidic channel 402 of FIG. 4A is in the form of a groove with straight sides. The microfluidic channel 452 of FIG. 4B is in the form of a cylindrical groove that forms an undercut 456 below the surface 430 of the tissue penetrator 300. The sizes of the openings 404 and 454 of the microfluidic channels 402 and 452, respectively, can be selected to achieve a desired payload-to-tissue contact area. Due to the undercut 456, the cylindrical microfluidic channel 452 can provide a larger volume for the same size opening relative to the straight-sided microfluidic channel 402.

[0034] The tissue penetrator can have microfluidic channels of uniform size and / or shape, or microfluidic channels of variable size and / or shape. The size of the microfluidic channels can range from a few microns in cross-sectional width to 500 microns or more in cross-sectional width. In some embodiments, the microfluidic channels are formed during 3D printing of the tissue penetrator. The microfluidic channels can extend the entire length of the tissue penetrator or only a portion of the length of the tissue penetrator. The microfluidic channels can be long relative to their width or diameter, such as having an aspect ratio of 500:1 or more, or short relative to their width or diameter, such as having an aspect ratio of about 1:1.

[0035] In some embodiments, the tissue penetrator may include multiple different cavity configurations, such as to accommodate different types of payloads. For example, the tissue penetrator may have a smaller cavity, such as smaller cavity volume or area 118, for loading a first payload and a larger cavity, such as larger cavity volume or area 118, for loading a second payload that is different from the first. 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.

[0036] 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 beneath the stratum corneum, a relatively large tissue penetrator can be constructed into an oral delivery device for implantation into the stomach lining, and even larger tissue penetrators 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 tip to the proximal end 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.

[0037] 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:

[0038] The cavity of the tissue penetrator can be configured to provide a desired total payload-to-tissue contact area for a given application. As discussed above, the total payload-to-tissue contact area can be adjusted to achieve a desired API release profile. The total payload-to-tissue contact area should be 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.

[0039] According to various embodiments, tissue penetrators are fabricated using one or more additive manufacturing processes. For example, with reference to FIG. 5 , one or more tissue penetrators 500 can be constructed on a 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. The cavities 502 can be formed by additive manufacturing processes, 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.

[0040] 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 into a first set of cavities, and a different type of payload 606 may be 3D printed into a second set of cavities 608.

[0041] 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 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 that pushes the tissue penetrator 702 into the tissue, e.g., driven by a spring positioned within the body 750. 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 can include a dissolvable catch that, when dissolved via interaction with stomach acid, releases the actuator to deploy the 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.

[0042] 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 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.

[0043] 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.

[0044] 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.

[0045] 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).

[0046] 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).

[0047] 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.

[0048] In some embodiments, the tissue penetrator material can be (or can include) a light-curable resin composed of (meth)acrylate-terminated absorbable polyester oligomers.

[0049] 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.

[0050] 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.

[0051] Although tissue penetrating devices are described above 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 with unfilled 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.

[0052] 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 its practical application, thereby enabling others skilled in the art to best utilize the technology and various embodiments, with various modifications suited to the particular use contemplated.

[0053] 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: A plurality of cavities; at least one payload including at least one active pharmaceutical ingredient (API), the at least one payload being loaded into the plurality of cavities such that the at least one API can be absorbed into the tissue when the at least one tissue-piercing member is implanted in the tissue; A drug delivery device, wherein the ratio of the surface area of ​​the plurality of cavities to the volume of the plurality of cavities is at least 0.5:

1.

2. The drug delivery device of claim 1 , wherein the plurality of cavities are arranged around a longitudinal axis of the at least one tissue-piercing member.

3. 3. The drug delivery device of claim 1, wherein the at least one payload comprises an excipient, and the ratio of the at least one API to the excipient in the payload is at least 2:

1.

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

5. The drug delivery device of claim 4 , wherein the at least one tissue-piercing member is 3D printed using stereolithography or material jetting.

6. The drug delivery device of any one of claims 1 to 5, wherein the at least one payload is 3D printed within the plurality of cavities.

7. The drug delivery device of any one of claims 1 to 6, wherein the at least one tissue-piercing member comprises a sharp tip for piercing the tissue.

8. The drug delivery device of any one of claims 1 to 7, wherein the at least one tissue-piercing member has an outer diameter of up to 2 millimeters.

9. The drug delivery device according to any one of claims 1 to 8, wherein the at least one payload has a total volume of at least 2 cubic millimeters.

10. 10. The drug delivery device of claim 9, wherein the total tissue contacting surface area of ​​the at least one payload is at least 20 square millimeters.

11. The drug delivery device of any one of claims 1 to 10, wherein the tissue is the stomach wall.

12. The drug delivery device of any one of claims 1 to 11, wherein the drug delivery device is configured for oral administration.

13. The drug delivery device of any one of claims 1 to 12, 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 payload.

14. The drug delivery device according to any one of claims 1 to 13, wherein a plurality of different APIs are loaded into said plurality of cavities.

15. 15. A method of delivering at least one API to tissue using the drug delivery device of any one of claims 1 to 14, comprising implanting the at least one tissue-piercing member into the tissue such that the at least one API can be absorbed into the tissue.

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