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: a plurality of lumens, and at least one payload comprising at least one active pharmaceutical ingredient (API) loaded into the plurality of lumens, the at least one tissue penetrating member is configured such that when the at least one tissue penetrating member is embedded in the tissue, the at least one API can be absorbed into the tissue wherein a ratio of a surface area of the plurality of lumens to a volume of the plurality of lumens is at least 0.5: 1.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 483,240, filed February 3, 2023, the entire contents of which are hereby incorporated by reference herein. 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] Tissue penetrating drug delivery device comprises multiple chambers, and these multiple chambers can be loaded with the effective load for delivering one or more API to tissue.Multiple chambers can be configured to provide desired release curve and / or increase drug effective load for effective load (that is, excipient and API).Multiple chambers can be configured to provide relatively high effective load and chamber contact area, which strengthens the retention of effective load in chamber, thereby allowing to use lower ratio of excipient in effective load, and thus increase the amount of API that can be loaded in tissue penetrating device.

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

[0008] The plurality of lumens may be arranged about a longitudinal axis of the at least one tissue penetrating member.The at least one payload may comprise an excipient, and the ratio of the at least one API to the excipient in the payload may be at least 2:1.

[0009] At least one tissue penetrating member can be 3D printed.At least one tissue penetrating member can be 3D printed using stereolithography or material jetting.At least one payload can be 3D printed into the plurality of cavities.

[0010] At least one tissue penetrating member may include a pointed tip for penetrating tissue.

[0011] At least one tissue penetrating member may have an outer diameter of at most 2 mm. At least one payload may have a total volume of at least 2 cubic millimeters. The total tissue contacting surface area of ​​at least one payload may be at least 20 square millimeters.

[0012] The at least one tissue penetrating member may be configured to penetrate into the stomach wall.The drug delivery device may be configured for oral administration.

[0013] At least one tissue penetrating member may include a plurality of microfluidic channels for retaining at least a portion of at least one payload.

[0014] A drug delivery device may have multiple different APIs loaded into multiple cavities.

[0015] According to one aspect, a method of delivering at least one API to tissue comprises using any of the above-described drug delivery devices. For example, the method may comprise inserting at least one tissue penetrating member into the tissue such that the at least one API can be absorbed into the tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0017] Figure 1A and Figure 1B An exemplary tissue penetrator comprising multiple lumens for loading with one or more APIs is shown;

[0018] Figure 2is an example of a conventional tissue penetrating member configuration;

[0019] Figure 3 An example of a tissue penetrator including a plurality of microfluidic channels is shown;

[0020] Figure 4A and Figure 4B is a cross-section of a portion of a tissue penetrator 300 illustrating an example of a possible configuration of a microfluidic channel;

[0021] Figure 5 An example of 3D printing of one or more tissue penetrators is shown;

[0022] 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;

[0023] Figure 7 An example of an oral delivery device comprising at least one tissue penetrator is shown; and

[0024] Figure 8 An example of a microneedle device comprising a plurality of tissue penetrators extending from a base is shown. DETAILED DESCRIPTION

[0025] 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 configuration of the multiple cavities can be selected to achieve different release profiles and / or increased drug payload.

[0026] 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. With this large contact area, the burden of providing adhesion forces on the excipient is reduced, which means that a given volume of payload can have a higher API to excipient ratio, thereby effectively increasing the API loading capacity of the tissue penetrator.

[0027] 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.

[0028] 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.

[0029] Figure 1A and Figure 1B An exemplary tissue penetrator 100 is shown, comprising a plurality of cavities 102 for loading one or more payloads, including one or more APIs. Tissue penetrator 100 is configured to penetrate the surface of tissue and embed into the tissue. Once embedded in the tissue, the API loaded in cavity 102 is absorbed into the surrounding tissue. As further explained below, the configuration of cavity 102 provides a high surface area of ​​payload-to-penetrator contact, which better retains the payload within the cavity, thereby requiring less excipient and a larger relative proportion of API in the payload.

[0030] Tissue penetrator 100 comprises main body 104, and cavity 102 is formed into this main body.Top 106 can be configured to penetrate into tissue, such as penetrate into skin or gastric mucosa.As shown, top 106 can be conical shape, or can comprise one or more bevels forming sharp tip top.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, and these one or more barbs or other prominent features 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 drug delivery device, such as intra-organ drug delivery device or orthopedic implant.Multiple tissue penetrators 100 can be mounted to substrate, such as transdermal patch or surgical mesh, for delivering one or more API simultaneously at multiple locations.

[0031] A plurality of cavities 102 are formed in the body 104 and are arranged about the longitudinal axis 105 of the tissue penetrator 100. A payload may be loaded into the cavity 102 for delivery to tissue. The payload may include one or more APIs and optional excipients. Figure 1A and Figure 1B , one of the cavities (cavity 102-A) loaded with payload 120 is shown.

[0032] The configuration of cavity 102 can be tailored to the desired volume of the payload and the exposed surface area of ​​the payload, factors that influence the amount of payload available for absorption into tissue and the rate of that absorption. Figure 1B 104 , the volume of each cavity 102 is defined by the area 118 of the cavity 102 at the surface 110 of the body 104 (which defines 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 can be straight or have a positive or negative draft angle. In the example shown, 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 cavity 102 can 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.

[0033] The shape, size, and number of cavities 102 can be customized 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, determined by the volume of the payload). Figure 1B A higher surface area to volume ratio can provide a faster release rate because more of the payload can come into contact with the surrounding tissue. For example, a higher surface area to volume ratio can be achieved by a greater number of shallower cavities.

[0034] Another advantage that lumen 102 of tissue penetrator 100 may provide is an increase in the drug to excipient ratio relative to conventional tissue penetrating members. Figure 2 An example of a conventional tissue penetrating member configuration is shown in . Conventional tissue penetrating member 200 includes a single large lumen 202 for loading a payload. Comparing tissue penetrating member 100 to conventional tissue penetrating member 200, the same lumen volume (and thereby the same payload volume) can be achieved, but with a much higher contact surface area between the surface of lumen 102 and the payload. In other words, the relatively large number of smaller lumens 102 of tissue penetrator 100 provides more contact area between the payload and lumen wall 112 than the single large lumen 202 of conventional tissue penetrating member 200. This greater contact area between the tissue penetrator and the payload results in a reduced need for an excipient to provide adhesion to hold the payload to tissue penetrator 100. As the contact surface area increases, an effective payload exposed surface area comparable to the effective payload exposed surface area of ​​conventional tissue penetrating member 200 can be achieved by reducing the excipient volume fraction (the exposed surface area of ​​the payload, e.g., by Figure 1B122 in the accompanying drawings). Relative to conventional tissue penetrating members 200, this relatively low required excipient volume fraction allows for a larger amount of API for the same payload volume.

[0035] Relative to Figure 2 1. The relatively high payload and lumen contact area provided by the tissue penetrator 100 of FIG. 1 can be illustrated by combining two designs configured to have a 2.5 mm 3 The contact area between the wall 204 of the lumen 202 of the conventional tissue penetrating member 200 and the payload loaded in the lumen 202 is about 0.13 mm 2 In comparison, the total contact area between the walls 112 and base 113 of the lumen 102 of the tissue penetrator 100 and the payload loaded in the lumen 102 is approximately 11.72 mm 2 . Thus, tissue penetrator 100 can be configured to provide approximately two orders of magnitude greater payload to lumen contact area relative to conventional designs for the same payload volume. Utilizing these exemplary comparative configurations and assuming that a conventional single lumen design requires a conventional 1:1 API to excipient ratio for retention in the lumen, tissue penetrator 100 can provide the same payload volume with greater than a 9:1 API to excipient ratio, meaning that for the same payload volume, tissue penetrator 100 can be loaded with nine times the amount of API as a conventional design. This increase in API loading capacity can be achieved without unduly increasing the payload exposed surface area (the surface area of ​​the payload that can come into contact with tissue) and, therefore, without unduly impacting the absorption rate. For example, in a case where a conventional design and tissue penetrator 100 are configured for a 2.5 mm 3 In the example of a total lumen volume of , the payload exposed surface area for a conventional tissue penetrating member 200 is approximately 22.45 mm 2 , and about 26.35 mm for tissue penetrator 100 2 .

[0036] Another advantage that the multiple lumens 102 of the tissue penetrator 100 may provide is that different APIs may be loaded into the same tissue penetrator. Figure 1B , the first cavity 102 -A may be loaded with a payload 120 having a first API or combination of APIs, and the second cavity 102 -B may be loaded with a different payload 124 having a second API or combination of APIs different from the first API.

[0037] Those skilled in the art will understand that the above Figure 1A and Figure 1BThe described lumen configurations are exemplary only, and the lumen 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 lumen surface area to lumen 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.

[0038] With the relatively high lumen surface area to lumen volume ratio of the penetrators described herein, suitable payloads can be loaded into the penetrator at an API to excipient ratio 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. The penetrator can be configured for payloads having an API to excipient ratio of at most 100: 1, at most 50: 1, at most 20: 1, at most 15: 1, or at most 10: 1.

[0039] although Figure 1A and Figure 1B The cavity 102 is shown as having a hexagonal shape with sides having positive draft angles, but this shape is merely exemplary, and it should be understood that the cavity can be any shape, such as cylindrical, conical, cubic, slotted, or irregular, and can have straight sides, curved sides, sides with negative draft angles, and any combination thereof. The cavity can be elongated, i.e., its major dimension extends in the direction of the longitudinal axis 105 of the penetrator 100, or can extend circumferentially about the longitudinal axis 105.

[0040] In some embodiments, the plurality of cavities may be or include a plurality of microfluidic channels. According to various embodiments, the microfluidic channels may be used in conjunction with a permeable material to generate a pressure gradient for delivering a payload to a tissue. The microfluidic channels may be used for fluid inlet and / or API outlet, which may be tailored to each specific payload. Additionally, microfluidic channels may be used when prolonged API release is desired.

[0041] Figure 3 An example of a tissue penetrator 300 is shown that includes a plurality of microfluidic channels 302 formed in rows extending longitudinally on a surface of a body 304 of the tissue penetrator 300. This configuration of microfluidic channels is merely exemplary, and one skilled in the art will appreciate that any desired arrangement of microfluidic channels may be formed in the body 304.

[0042] Figure 4A and Figure 4B yes Figure 3 A cross-section of a portion of a tissue penetrator 300 showing a microfluidic channel (such as Figure 3 Examples of possible configurations of microfluidic channels 302). Figure 4A The microfluidic channel 402 is in the shape of a straight-sided groove. Figure 4B The microfluidic channel 452 is in the shape of a cylindrical recess 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-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.

[0043] The tissue penetrator can have microfluidic channels of uniform size and / or shape or microfluidic channels of varying size and / or shape. The dimensions of the microfluidic channels can range from a cross-sectional width of a few microns up to a cross-sectional width of 500 microns or greater. 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 can extend 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 greater, or can be short relative to their width or diameter, such as having an aspect ratio of approximately 1:1.

[0044] In some embodiments, a tissue penetrator can include multiple different lumen configurations, such as to accommodate different types of payloads. For example, a tissue penetrator can have a smaller lumen, such as smaller lumen volume or area 118, for loading a first payload, and a larger lumen, such as larger lumen volume or area 118, for loading a second payload different from the first payload. This arrangement can provide for the delivery of different APIs, different amounts of APIs, and / or APIs at different release rates using the same tissue penetrator.

[0045] 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 tip 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.

[0046] 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.

[0047] The lumen of the tissue penetrator can be configured to provide the total payload to tissue contact area required for a given application. As described 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 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 .

[0048] According to various embodiments, the tissue penetrator is made using one or more additive manufacturing processes. Figure 5 , one or more tissue penetrators 500 may 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 may be formed using an additive manufacturing process that may allow 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 a tissue penetrator, and / or microfluidic channels are features that may be formed in a tissue penetrator using additive manufacturing that may not be possible using other manufacturing techniques.

[0049] In some embodiments, the payload is formed into the cavity during the additive manufacturing process. Figure 6An 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.

[0050] As described above, various embodiments of tissue penetrators may be incorporated into various drug delivery devices for a variety of different applications. Figure 7 An example of an oral delivery device 700 is shown, which 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. The oral delivery device 700 may include a main body 750 to which the tissue penetrator 702 is attached. The main body 750 may be configured for oral administration and delivery through the digestive tract to a desired location in the tissue 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 the 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 the desired location. For example, the main body 750 may include a dissolvable trap that, when dissolved by interaction with gastric acid, releases an actuator that deploys one or more tissue penetrators. The tissue penetrator 702 may be configured to passively drop out of the tissue after a period of time, or may be configured to dissolve over time.

[0051] Figure 8 An example of a microneedle device 800 is shown, which includes a plurality of tissue penetrators 802 extending from a base 850 to be embedded in tissue 860. Microneedle device 800 can be, for example, a patch, an orthotic 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.

[0052] 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.

[0053] 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).

[0054] 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).

[0055] 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).

[0056] 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.

[0057] In some embodiments, the tissue penetrator material can be (or include) a photocurable resin composed of a (meth)acrylate-terminated absorbable polyester oligomer.

[0058] 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.

[0059] 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.

[0060] 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.

[0061] 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.

[0062] Although the present disclosure and examples have been fully described with reference to the accompanying drawings, it should be noted that various changes and modifications will become apparent to those skilled in the art. Such changes and modifications are to be understood as being included within the scope of the present disclosure and examples as defined by the claims. Finally, the entire disclosures of the patents and publications mentioned in this application are 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: Multiple cavities, and at least one payload, the at least one payload comprising 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 is capable of being absorbed into the tissue when the at least one tissue penetrating member is embedded in the tissue, wherein a 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 according to claim 1, wherein The plurality of lumens are arranged about a longitudinal axis of the at least one tissue penetrating member.

3. The drug delivery device according to claim 1 or claim 2, 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. A drug delivery device according to any one of the preceding claims, wherein The at least one tissue penetrating member is 3D printed.

5. The drug delivery device according to claim 4, wherein: The at least one tissue penetrating member is 3D printed using stereolithography or material jetting.

6. A drug delivery device according to any one of the preceding claims, wherein: The at least one payload is 3D printed into the plurality of cavities.

7. 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.

8. 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.

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

10. The drug delivery device according to claim 9, wherein: The at least one payload has a total tissue contacting surface area of ​​at least 20 square millimeters.

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

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

13. 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 payload.

14. A drug delivery device according to any one of the preceding claims, wherein: A plurality of different APIs are loaded into the plurality of cavities.

15. A method of delivering at least one API to a tissue using the drug delivery device according to any one of claims 1 to 14, the method comprising: The at least one tissue penetrating member is embedded in the tissue such that the at least one API can be absorbed into the tissue.

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