WO2024163831A1

WO2024163831A1 - Devices and methods for delivering a drug via an api-loaded tissue penetrator

Info

Publication number: WO2024163831A1
Application number: PCT/US2024/014131
Authority: WO
Inventors: Peyton HOPSON; Stephen G. Gara; Drake SMALLEY
Original assignee: Janssen Biotech, Inc.
Priority date: 2023-02-03
Filing date: 2024-02-02
Publication date: 2024-08-08

Abstract

A drug delivery device includes a substrate; and a plurality of tissue penetrating members 3D printed onto the substrate and configured to embed into tissue, wherein at least one of the plurality of tissue penetrating members is configured to anchor the drug delivery device to the tissue; and at least one payload comprising at least one API loaded into at least one of the substrate and the plurality of tissue penetrating members for absorbing into the tissue when the at least one tissue penetrating member is embedded in the tissue.

Description

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

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63/483,244, filed February 3, 2023, the entire contents of which are hereby incorporated by reference herein.

FIELD

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

BACKGROUND

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

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

[0005] According to an aspect, a drug delivery device includes one or more tissue penetrators that anchor the drug delivery device to tissue so that the drug delivery device can deliver one or more APIs to the tissue. The drug delivery device can include a substrate and a plurality of tissue penetrators 3D printed to the substrate, at least some of which are configured to anchor the substrate to the tissue. One or more payloads that include one or more APIs can be loaded to the substrate and/or one or more tissue penetrators for absorbing into the tissue when the drug delivery device is anchored to the tissue. An anchoring tissue penetrator can include at least one extender configured to move from a retracted position to an extended position within the tissue to anchor the tissue penetrator in the tissue.

[0006] According to an aspect, a drug delivery device includes a substrate; and a plurality of tissue penetrating members 3D printed onto the substrate and configured to embed into tissue, wherein at least one of the plurality of tissue penetrating members is configured to anchor the drug delivery device to the tissue; and at least one payload comprising at least one API loaded into at least one of the substrate and the plurality of tissue penetrating members for absorbing into the tissue when the at least one tissue penetrating member is embedded in the tissue.

[0007] The at least one of the plurality of tissue penetrating members may include at least one barb for preventing pullout of the at least one of the plurality of tissue penetrating members.

[0008] The at least one of the plurality of tissue penetrating members may include a curved tissue penetrating end for retaining the at least one of the plurality of tissue penetrating members in the tissue.

[0009] The substrate may include a patch, a plate, a mesh, or a hydrogel.

[0010] Optionally, a first set of the plurality of tissue penetrating members are configured for anchoring the drug delivery device to the tissue and a second set of the plurality of tissue penetrating members are configured to hold at least a portion of the at least one payload.

[0011] The plurality of tissue penetrating members may be 3D printed onto the substrate using stereolithography or material jetting. [0012] The at least one of the plurality of tissue penetrating members may have an outer diameter of up to 2 millimeters.

[0013] According to an aspect, a method of delivering a drug to tissue includes embedding a plurality of tissue penetrating members of a drug delivery device into the tissue, the plurality of tissue penetrating members 3D printed onto a substrate, anchoring the drug delivery device into the tissue via at least one of the plurality of tissue penetrating members; and releasing at least one API that is loaded into at least one of the substrate and the plurality of tissue penetrating members into the tissue as the drug delivery device is anchored in the tissue.

[0014] The at least one of the plurality of tissue penetrating members may include at least one barb for preventing pullout of the at least one of the plurality of tissue penetrating members. The at least one of the plurality of tissue penetrating members may include a curved tissue penetrating end for retaining the at least one of the plurality of tissue penetrating members in the tissue.

[0015] The substrate may include a patch, a plate, a mesh, or a hydrogel.

[0016] The method may include anchoring the drug delivery device to the tissue by a first set of the plurality of tissue penetrating members and releasing the at least one API from a second set of the plurality of tissue penetrating members.

[0017] The plurality of tissue penetrating may have been 3D printed onto the substrate using stereolithography or material jetting.

[0018] The at least one of the plurality of tissue penetrating members may have an outer diameter of up to 2 millimeters.

[0019] According to an aspect, a method of making a drug delivery device includes 3D printing a plurality of tissue penetrating members onto a substrate, the plurality of tissue penetrating members configured to embed into tissue, wherein at least one of the plurality of tissue penetrating members is configured to anchor the substrate to the tissue; and loading at least one of the substrate and the plurality of tissue penetrating members with a payload that comprises at least one API for absorbing into the tissue when the at least one tissue penetrating member is embedded in the tissue. [0020] The at least one of the plurality of tissue penetrating members may include at least one barb for preventing pullout of the at least one of the plurality of tissue penetrating members. The at least one of the plurality of tissue penetrating members may include a curved tissue penetrating end for retaining the at least one of the plurality of tissue penetrating members in the tissue.

[0021] The substrate may include a patch, a plate, a mesh, or a hydrogel.

[0022] A first set of the plurality of tissue penetrating members may be configured for anchoring the drug delivery device to the tissue and a second set of the plurality of tissue penetrating members may be configured to hold at least a portion of the at least one payload.

[0023] The plurality of tissue penetrating members may be 3D printed onto the substrate using stereolithography or material jetting.

[0024] The at least one of the plurality of tissue penetrating members may have an outer diameter of up to 2 millimeters.

[0025] According to an aspects, a drug delivery device for attaching to tissue includes at least one tissue penetrating member configured to embed into tissue, the at least one printed tissue penetrating member comprising: a main body that comprises a distal end for piercing the tissue, and at least one extender that is connected to the main body, wherein the at least one extender is configured to move relative to the main body from a retracted position to an extended position, wherein when the at least one tissue penetrating member is embedded in the tissue and the at least one extender is in the extended position, the at least one extender anchors the at least one tissue penetrating member in the tissue.

[0026] The main body and the at least one extender may be 3D printed as a single piece. The main body and at least one extender may be 3D printed using at least one of stereolithography (SL) and material jetting (MJ).

[0027] The at least one extender may be connected to the main body by a living hinge. The living hinge and the at least one extender may be formed of the same material. The living hinge and the at least one extender may be formed of different materials. [0028] The at least one extender may be configured to retract as the at least one extender moves past an outer surface of the tissue during insertion of the at least one tissue penetrating member into the tissue and extend after the at least one extender has moved past an outer surface of the tissue.

[0029] The at least one extender may be connected to a collar that is movably mounted to the main body and movement of the collar toward the distal end may move the at least one extender to the extended position.

[0030] The collar may be configured to move in response to a force that exceeds an insertion force threshold such that a force applied to the collar that is less than the insertion force threshold can cause insertion of the at least one tissue penetrating member into the tissue without causing movement of the at least one extender to the extended position and a force applied to the collar that is higher than the insertion force threshold can cause the at least one extender to move to the extended position.

[0031] The at least one tissue penetrating member may have an outer diameter of up to 2 millimeters.

[0032] According to an aspect, a method of delivering a drug to tissue includes inserting at least a portion of at least one tissue penetrating member of a drug delivery device into the tissue; moving at least one extender of the at least one tissue penetrating member while the at least one extender is located within the tissue from a retracted position to an extended position to anchor the drug delivery device in the tissue; and releasing at least one API loaded into the drug delivery device into the tissue as the drug delivery device is anchored in the tissue.

[0033] The at least one extender may be 3D printed as a single piece with a main body of the at least one tissue penetrating member. The main body and at least one extender may be 3D printed using at least one of stereolithography (SL) and material jetting (MJ).

[0034] The at least one extender may be connected to a main body by a living hinge. The living hinge and the at least one extender may be formed of the same material. The living hinge and the at least one extender may be formed of different materials. [0035] The at least one extender may retract as the at least one extender moves past an outer surface of the tissue during insertion of the at least one tissue penetrating member into the tissue and extend after the at least one extender has moved past an outer surface of the tissue.

[0036] The at least one extender may be connected to a collar that is movably mounted to a main body, and moving the at least one extender from a retracted position to an extended position to anchor the drug delivery device in the tissue may include moving the collar toward a distal end of the at least one tissue penetrating member to move the at least one extender to the extended position.

[0037] Optionally, inserting the at least a portion of at least one tissue penetrating member of a drug delivery device into the tissue includes applying an insertion force to the collar to cause insertion of the at least one tissue penetrating member into the tissue without causing movement of the at least one extender to the extended position, and wherein a force applied to the collar to move the at least one extender to the extended position exceeds the insertion force applied to the collar.

[0038] The at least one tissue penetrating member may have an outer diameter of up to 2 millimeters.

[0039] According to an aspect, a drug delivery device for targeting unhealthy tissue that has lower strength than healthy tissue of the same type includes at least one tissue penetrating member configured to penetrate the unhealthy tissue when a penetration force is applied to the at least one tissue penetrator and fail to penetrate the healthy tissue when the penetration force is applied to the at least one tissue penetrator.

[0040] According to an aspect, a drug delivery device for targeting unhealthy tissue that has higher strength than healthy tissue of the same type includes at least one tissue penetrating member configured to penetrate into the healthy tissue and the unhealthy tissue and comprising one or more anchors that is configured to anchor the at least one tissue penetrating member to the unhealthy tissue but fail to anchor the at least one tissue penetrating member to the healthy tissue BRIEF DESCRIPTION OF THE FIGURES

[0041] The invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0042] FIG. 1 illustrates a drug delivery device that is configured to anchor to tissue to deliver one or more APIs to the tissue;

[0043] FIG. 2 is an enlarged view of an anchoring tissue penetrator shown in FIG. 1;

[0044] FIG. 3 illustrates a portion of an exemplary anchoring tissue penetrator that includes movable extenders;

[0045] FIG. 4 illustrates an example of a drug delivery device that includes one or more anchoring tissue penetrators for selectively targeting relatively weak unhealthy tissue;

[0046] FIG. 5 illustrates an example of 3D printing of one or more tissue penetrators;

[0047] FIG. 6 illustrates an example of the 3D printing of a tissue penetrator in which a payload is 3D printed into the cavities of the tissue penetrator;

[0048] FIG. 7 illustrates an example of an oral delivery device that includes at least one tissue penetrator; and

[0049] FIG. 8 illustrates an example of a microneedle device that includes a plurality of tissue penetrators that extend from a substrate.

DETAILED DESCRIPTION

[0050] Described herein are drug delivery devices that include tissue penetrators that can embed in tissue to deliver one or more APIs to the tissue and methods of drug delivery using the drug delivery devices. One or more of the tissue penetrators can be configured for anchoring the device in the tissue. For example, one or more tissue penetrators can include one or more anchoring features, such as one or more barbs or other type of projections, that resist pull-out of the tissue penetrator from the tissue. The device can include one or more tissue penetrators 3D printed onto a substrate, where one or more of the tissue penetrators is configured for anchoring the device to the tissue. One or more APIs can be loaded to the substrate and/or one or more of the tissue penetrators, such as in one or more cavities of the tissue penetrators, for absorbing into the tissue as the device is anchored to the tissue.

[0051] The inclusion of anchoring features in the tissue penetrators may eliminate or at least reduce reliance on tissue frictional forces and/or adhesives for retaining the drug delivery device to the tissue. Anchoring features can be included as either as a single anchoring feature or a plurality of anchoring features. Generally, an anchoring feature is configured to expand tissue either during or after insertion and for the tissue to collapse behind the anchoring feature, which provides the necessary resistance to withdrawal of the tissue penetrator that keeps the tissue penetrator embedded in the tissue. Generally, the size and leading edge angle of the anchoring feature and the number of the anchoring features of a tissue penetrator will be dependent on the nominal density of the tissue, the tissue strength, and the mechanical properties of the tissue penetrator. The anchoring feature can be configured to minimize tissue damage during insertion as the tissue is compressed at the leading surface of the anchoring feature.

[0052] According to an aspect, anchoring feature(s) may be tailored to the condition of the tissue targeted for the one or more APIs. This can enable tissue specificity in the case where the one or more APIs are intended to target a compromised tissue area within the body, such as a tissue area that has reduced density, reduced strength, etc. For example, the tissue penetrating leading surface and/or other mechanical aspects of the tissue penetrator can be designed to apply a relatively low insertion force to the tissue such that only the targeted compromised tissue can be penetrated. The one or more anchoring feature(s) are configured to retain the tissue penetrator in the targeted tissue.

[0053] The inclusion of one or more anchoring features may provide a number of advantages, including eliminating the need for external fixation devices or adhesives for tissue retention, enabling tissue selectivity, enabling retention in a larger range of compromised tissue (e.g., reduced strength and/or density tissue due to illness, infection, etc.), and decoupling of the tissue penetrator retention force from the penetration force.

[0054] Reference will now be made in detail to implementations and embodiments of various aspects and variations of devices, systems and methods described herein. Although several exemplary variations of the devices, systems and methods are described herein, other variations of the devices, systems and methods may include aspects of the devices, systems and methods described herein combined in any suitable manner having combinations of all or some of the aspects described.

[0055] In the following description, it is to be understood that the singular forms “a,” “an,” and “the” used in the following description are intended to include the plural forms as well, unless the context clearly indicates otherwise. It is also to be understood that the term “and/or” as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. It is further to be understood that the terms “includes, “including,” “comprises,” and/or “comprising,” when used herein, specify the presence of stated features, integers, steps, operations, elements, components, and/or units but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, units, and/or groups thereof.

[0056] FIG. 1 illustrates a drug delivery device 100 that is configured to anchor to tissue to deliver one or more APIs to the tissue. The drug delivery device 100 includes one or more tissue penetrating members 104 extending from a substrate 102, such as a transdermal patch, a surgical mesh, an orthopedic plate, a hydrogel, or other type of substrate, for simultaneously delivering one or more APIs at multiple locations. Each tissue penetrator 104 is configured to penetrate a surface of tissue and embed into the tissue. At least one of the tissue penetrators — tissue penetrators 104- A — is configured to anchor to the tissue. The anchoring tissue penetrators 104-A are configured to resist pullout from the tissue, such as by including one or more barbs 110 or other projecting features, as discussed further below.

[0057] Optionally, the drug delivery device 100 may include one or more tissue penetrators that are not configured for anchoring to the tissue, such as non-anchoring tissue penetrators 104-B included in the embodiment illustrated in FIG. 1. Non-anchoring tissue penetrators 104-B may be configured primarily for delivering one or more APIs to the tissue. The non-anchoring tissue penetrators 104-B extend from the substrate 102 such that when the substrate 102 is pushed on a desired surface of the tissue during use, the anchoring tissue penetrators 104-A and non-anchoring tissue penetrators 104-B penetrate into the tissue.

[0058] One or more payloads comprising one or more APIs can be loaded to one or more of the tissue penetrators 104 and/or to the substrate 102. For example, the non-anchoring tissue penetrators 104-B can be loaded with one or more payloads 106 comprising one or more APIs. When the non-anchoring tissue penetrators 104-B are embedded in the tissue, the one or more APIs loaded to the non-anchoring tissue penetrators 104-B absorb into the tissue. Optionally, payload comprising one or more APIs can be loaded to the anchoring tissue penetrator 104-A. Additionally or alternatively, one or more payloads 108 comprising one or more APIs can be loaded to the substrate 102 for absorbing through the surface of the tissue to which the drug delivery device 100 is anchored.

[0059] According to various embodiments, during use, the substrate 102 may be pushed onto a desired surface of the tissue until one or more tissue penetrators 104, which includes one or more anchoring tissue penetrators 104-A, embed into the tissue. The anchoring tissue penetrator(s) 104- A anchor the drug delivery device 100 to the tissue such that the drug delivery device 100 does not detach from the tissue without a sufficient detachment force being applied to the drug delivery device 100. While anchored, one or more APIs are absorbed into the tissue, such as from a payload loaded to one or more anchoring tissue penetrators 104-A, one or more non-anchoring tissue penetrators 104-B, and/or the substrate 102.

[0060] The drug delivery device 100 can be configured with any number of tissue penetrators 104 depending on the requirements of a given application, including any number of anchoring tissue penetrators 104-A and any number (or no) of non-anchoring tissue penetrators 104-B. The number of anchoring tissue penetrators 104-A is generally selected to provide sufficient anchoring force and to provide anchoring at sufficient spatial locations and generally depends on the size of the substrate and the amount of retention provided by each anchoring tissue penetrator 104-A. In the illustrated embodiment, anchoring tissue penetrators 104-A are provided at each corner of the substrate 102 to hold the entire substrate against the tissue. However, this is merely exemplary and it should be understood that fewer or greater numbers of anchoring tissue penetrators 104-A may be used.

[0061] The number of non-anchoring tissue penetrators 104-B, if any, may be selected to provide the desired amount of loading capacity for one or more APIs and/or to provide the desired API absorption locations. In some variations, the drug delivery device does not have any nonanchoring tissue penetrators 104-B, in which case the one or more APIs may be loaded to one or more of the anchoring tissue penetrators 104-A and/or to the substrate 102. [0062] FIG. 2 is an enlarged view of the anchoring tissue penetrator 104-A of FIG. 1. A distal portion 122 of a body 120 of the anchoring tissue penetrator 104-A is configured for penetrating into tissue, such as into the skin or stomach lining. The distal portion 122 can include one or more bevels 124 that meet at a pointed tip 126 for piercing tissue. The body 120 and/or distal portion 122 can be straight or can be curved as illustrated, which can help better retain the anchoring tissue penetrator 104-A in the tissue relative to, for example, a straight body and/or tip.

[0063] One or more barbs 110 or other projecting features may project from the body to help retain the tissue penetrator in the tissue. The one or more barbs 110 may be designed to minimize tissue damage during insertion as the tissue is compressed at the leading surface 111 of the barb 110. For example, the leading surface angle 113 and other geometry of the barb 110 may be selected to minimize tissue damage. Upon insertion into tissue, the tissue behind the barb 110 will tend to collapse around the body 120. Movement of the tissue penetrator 104-A in the direction opposite the insertion direction will cause the tissue behind the barb 110 to be snagged by the barb 110, which serves to resist the movement of the anchoring tissue penetrator 104-A out of its embedded position in the tissue. To withdraw the anchoring tissue penetrator 104-A from the tissue, a withdrawal force would need to be applied to the anchoring tissue penetrator 104-A that is sufficient to dislodge the tissue snagged behind the barb 110, such as by tearing the tissue. The shape, size, and material of the barb can be selected to tune the withdrawal force to a desired amount. Generally, the size and leading surface angle of the barb(s) 110 and the number of the barbs will be dependent on the density of the tissue, the tissue strength, and the mechanical properties of the barb(s) 110.

[0064] In some variations, the barb 110 or other projecting feature is made of a flexible material such that it can retract toward the body 120 as the barb 110 moves past an outer surface of the tissue when the anchoring tissue penetrator 104-A is being inserted into the tissue. The flexible barb could then extend back away from the body 120 after moving past the outer surface of the tissue and/or could be forced back to an extended position by the tissue that has collapsed behind should the body 120 be pulled in reverse of the insertion direction. In some variations, the barb 110 or other projecting feature is connected to the body 120 by flexible material, such as a living hinge, such that the barb 110 can retract — e g., collapse toward the body 120 — during insertion and then extend outwardly away from the body 120 for preventing pullout of the tissue penetrator. [0065] The anchoring tissue penetrator 104-A can include one or more cavities 128 formed in the body 102 for loading with a payload 130 that includes one or more APIs. As noted above, when the anchoring tissue penetrator 104-A is embedded in the tissue, the one or more APIs can absorb into the surrounding tissue.

[0066] The shape, size, and number of cavities 128 can be tailored for a given application to provide a desired release profile and/or payload volume. Cavities can be any shape, such as cylindrical, conical, cubic, slot-shaped, or irregularly shaped, and can have straight sides, curved sides, sides with negative draft angles, and any combinations thereof.

[0067] In some embodiments, a tissue penetrator may include multiple different cavity configurations, such as to accommodate different types of payloads. For example, a tissue penetrator may have smaller cavities, such as a smaller cavity volume or cavity opening, for loading with a first payload and larger cavities, such as a larger cavity volume or cavity opening, for loading with a second payload that is different from the first. This arrangement can provide for delivery of different APIs, different quantity of APIs, and/or different release rates of APIs with the same tissue penetrator.

[0068] FIG. 3 illustrates a portion of an exemplary anchoring tissue penetrator 300 that can be used for the anchoring tissue penetrators 104-A of drug delivery device 100 of FIG. 1. As described further below, anchoring tissue penetrator 300 include one or more extenders that extend when the anchoring tissue penetrator 300 is embedded in tissue to resist pullout of the anchoring tissue penetrator 300 from the tissue.

[0069] Anchoring tissue penetrator 300 includes a body 302, a distal portion 304 of which is configured for penetrating into tissue. For example, the distal portion 304 can be shaped to form a pointed tip 306. Located proximally of the distal portion 304 are one or more extenders 308, each of which is connected to the body 302 at a first hinge 310 that enables the extender 308 to extend away from the body 302 and retract toward the body 302.

[0070] The extender 308 includes a first arm 312 and a second arm 314 that is hingedly connected to the first arm 312 at a second hinge 316. The second arm 314 can be connected to a collar 318 by a third hinge 320. The collar 318 is slidably mounted to a shaft 322 of the body 302, which extends between the distal portion 304 of the body 302 and a proximal portion 324 of the body 302. The collar 318 can slide in a direction of the longitudinal axis 326 of the body 302 along the shaft 322. When the collar 318 slides distally, as indicated by arrow 328, the collar 318 causes the second arm 314 to pivot about the hinge 320 such that the end of the second arm 314 that is connected via second hinge 316 to the first arm 312 moves outward, away from the body 302. The first arm 312 also pivots outwardly away from the body 302, as indicated by arrow 330. As the collar 318 continues to slide distally, the second arm 314 may continue to pivot until it extends perpendicularly to the longitudinal axis 328 and, optionally, past perpendicular.

[0071] One or more of the first hinge 310, second hinge 316, and third hinge 320 can be formed as a mechanical hinge or a living hinge. The living hinge can be formed of the same material as the extender material and/or body material but have less material thickness at the hinge (as shown in the embodiment of FIG. 3) or can be made of a different, lower strength material (with or without reduced thickness).

[0072] During use, the anchoring tissue penetrator 300 is forced into tissue. As the one or more extenders 308 move past an outer surface of the tissue, the force applied by the tissue to the outer sides of the first arms 312 will force the extenders 308 to retract or collapse toward the body 302. The collar 318 will slide proximally on the shaft 322 as the extenders 308 collapse. The degree to which the extenders 308 collapse may be controlled by the amount of proximal travel allowed for the collar 318. For example, the collar 318 travel may be limited at the proximal end of the shaft 322 by a stop 332. The anchoring tissue penetrator 300 may be inserted into the tissue at least until the tissue extender 308 is fully embedded in the tissue.

[0073] In some examples, when the anchoring tissue penetrator 300 is fully embedded in the tissue, the extenders 308 may extend outwardly sufficiently such should a withdrawal force be applied to the anchoring tissue penetrator 300 (a force tending to withdraw the tissue penetrator from its embedded position), contact between the surrounding tissue and the second arms 314 may push the second arms 314 distally relative to the shaft 322, forcing the extenders 308 to extend outwardly. This extension creates more anchoring force, making it harder to withdraw the anchoring tissue penetrator 300. [0074] In some examples, the extenders 308 are extended once the anchoring tissue penetrator 300 is embedded in the tissue, such as by a force applied to the collar 318 that causes the collar 318 to move distally on the shaft 322. In some embodiments, the force can be applied to collar 318 by body 302 moving distally on the shaft 322. This causes the extenders 308 to extend outwardly. The collar 318 may be configured to extend out past a surface of the tissue when the anchoring tissue penetrator 300 is embedded in the tissue such that a user can access the collar 318 (e.g., directly or using a tool) to move the collar distally for extending the extenders 308. In some embodiments, the collar 318 can be used both for insertion and for extension of the extenders 308. The collar 318 and extenders 308 can be configured such that a force required to extend the extenders 308 is greater than the range of insertion forces required to insert the tissue penetrator 300 into the desired tissue. An insertion force can be applied to the collar 318 to insert the tissue penetrator 300 into the tissue. Then, once inserted, an extension force that is higher than the insertion force can be applied to the collar 318 to move the collar 318 distally to extend the extenders 308. Further penetration of the tissue penetrator 300 while the extension force is applied can be limited by, for example, a substrate (e.g., substrate 102 of FIG. 1) or other feature of the drug delivery device contacting the outer surface of the tissue. Optionally, the collar 318 can be moved proximally (such as by a user) to collapse the extenders 308 and allow withdrawal of the anchoring tissue penetrator 300 from the tissue.

[0075] In some examples, the extender 308 does not include the second arm 304 and collar 318 such that the extender 308 includes just the first arm 312, which is outwardly biased. During insertion, the tissue (e.g., the surface of the tissue) collapses the first arm 312 toward the body 302. Once the first arm 312 is past the surface of the tissue and/or upon any reverse movement of the anchoring tissue penetrator 300 in a direction out of the tissue, the first arm 312 extends outwardly, such as due to the outward bias and/or due to tissue proximal of the proximal ends of the first arm 312 being snagged by the proximal ends of the first arm 312, which resists further withdrawal of the anchoring tissue penetrator 300.

[0076] Tissue penetrators can be configured for selective targeting of unhealthy, or otherwise compromised, tissue for delivery one or more APIs to the targeted tissue. For example, the tissue penetrating distal end of the tissue penetrator can be configured such that relatively weak tissue, such as tissue in an unhealthy, diseased, or otherwise compromised state (e.g., tissue with reduced strength and/or density due to illness, infection, etc.), can be penetrated but healthy tissue cannot be penetrated. In some variations, the force required to penetrate healthy tissue by the tissue targeting tissue penetrator may be higher than the insertion force applied to the tissue penetrator during use and/or the force required to penetrate healthy tissue may be greater than, for example, a force that the tissue penetrator can withstand without failing such that the tissue penetrator is incapable of penetrating healthy tissue. In contrast, the tissue penetrator may be configured such that it can penetrate relatively weak compromised tissue. The tissue penetrator includes one or more anchoring features, according to the principles described herein, to anchor the tissue penetrator in the relatively weak tissue since the weak tissue is likely to provide relatively little resistance to pull-out of the tissue penetrator.

[0077] FIG. 4 illustrates an example of a drug delivery device 400 that includes one or more anchoring tissue penetrators 402 that target relatively weak tissue 450 such that one or more APIs can be delivered to the relatively weak tissue 450. The relatively weak tissue 450 may be adjacent to relatively strong tissue 460 that is not intended to receive the one or more APIs. The relatively weak tissue 450 may be tissue of a different type that is mechanically weaker than the relatively strong tissue 460 and/or can be the same type of tissue but in a weakened state, such as due to trauma or disease.

[0078] The tissue penetrators 402 can include relatively blunted tips 404 that are configured to penetrate into the targeted relatively weak tissue 450 and to be incapable of penetrating into the relatively strong tissue 460 under normal use. The tissue penetrators 402 are configured such that the force that would otherwise be required to push the blunted tip 404 into the relative strong tissue 460 is higher than a failure force of the anchoring tissue penetrator 402, such that the anchoring tissue penetrator 402 fails (e.g., buckles, breaks, bends, etc.) without being able to penetrate into the relative strong tissue 460 (or not able to sufficiently penetrated to anchor to the tissue and/or deliver payload to the tissue). For example, with reference to FIG. 2, the main body 120 of anchoring tissue penetrator 104- A may be configured to bend or break prior to the tip 126 penetrating into non-targeted tissue or prior to the one or more barbs 110 penetrating into the tissue.

[0079] In the illustrated example, the drug delivery device 400 includes two anchoring tissue penetrators 402-A and 402-B that extend from a main body 430. The first tissue penetrator 402- A has penetrated into the relative weak tissue 450 but the second tissue penetrator 402-B was incapable of penetrating the relative strong tissue 460 before buckling from the insertion force applied to the drug delivery device 400. The anchoring tissue penetrators 402 include one or more anchoring features 408, according to the principles described herein, which help anchor the tissue penetrators 402 in the relative weak tissue 450. In some examples, the anchoring tissue penetrators 402 may be loaded with one or more APIs for delivery to the targeted relatively weak tissue 450.

[0080] Alternatively, an anchoring tissue penetrator could be configured to anchor to unhealthy tissue that is relatively stronger than healthy tissue of the same type while being unable to anchor to the healthy tissue. Certain conditions, such as fibrosis or inflammation, may cause tissue to become denser and, thereby, stronger in terms of its ability to retain a tissue penetrator. A tissue penetrator could be configured to selectively target the denser (or otherwise stronger) unhealthy tissue by including anchoring features that the unhealthy tissue can hold onto but that the healthy tissue (having lower strength) cannot. The tissue penetrator can penetrate into both the healthy and the unhealthy tissue, but in the healthy tissue, the tissue penetrator will pull out because it is unable to anchor to the relatively weak tissue. A tissue penetrator may be configured to selectively target stronger unhealthy tissue by configuring the anchoring feature(s) to have a lower anchoring strength, such as by reducing an amount of extension of, for example, a barb or set of extenders. For example, with reference to anchoring tissue penetrator 104-A of FIGS. 1 and 2, the barb 110 may be configured such that the amount of tissue collapsed behind it after insertion will have sufficient retention strength when the tissue is in a compromised state (e.g., that is targeted by the one or more APIs) that causes the tissue to be stronger than when in the uncompromised state, but insufficient retention strength when the tissue is in the uncompromised state such that the tissue penetrator can pull out of the uncompromised tissue. As such, the tissue penetrator will anchor the drug delivery device to the compromised tissue for delivery of the one or more APIs loaded to the drug delivery device, while being unable to anchor the drug delivery device to uncompromised tissue that is not intended to receive the one or more APIs. In other embodiments, tissue penetrating members targeting the unhealthy tissue may comprise barbs or extenders requiring a high insertion force to deploy into their extended states to anchor into the unhealthy tissue. Accordingly, insertion into healthy tissue, which would require a force less than the deploying force of the barbs or extenders, would not anchor the tissue penetrating members, facilitating removal and avoiding unnecessary delivery of API into the healthy tissue. [0081] A surgical mesh might target a lower density tissue or possibly a gradient of densities for wound closure. A device may include different tissue penetrator configurations for targeting different tissue densities. For example, a mesh could have a matrix of different tissue penetrator configurations for targeting different densities across the mesh.

[0082] Tissue penetrators, including any of the tissue penetrator described above, can be sized according to a given application, such as for achieving a desired penetration depth and/or for achieving a desired total payload volume. For example, a plurality of relatively small tissue penetrators, often referred to as microneedles, can be mounted to a patch and pressed into the skin for API delivery into the skin, such as beneath the stratum corneum, relatively larger tissue penetrators can be built into oral delivery devices for embedding into the stomach lining, and still larger tissue penetrators can be configured for orthopedic application in which the tissue penetrators embed into bone. Tissue penetrators can have a range of different diameters. For example, tissue penetrators can have diameters that correspond with diameters of standard hypodermic needle gauges. For example, a tissue penetrator can have a diameter corresponding to hypodermic needle gauge of 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, or 34, corresponding to an outside diameter of about 4.57 mm, 4.19 mm, 3.76 mm, 3.40 mm, 3.05 mm, 2.77 mm, 2.41 mm, 2.11 mm, 1.83 mm, 1.65 mm, 1.47 mm, 1.27 mm, 1.07 mm, 0.91 mm, 0.82 mm, 0.72 mm, 0.64 mm, 0.57 mm, 0.51 mm, 0.46 mm, 0.41 mm, 0.36 mm, 0.34 mm, 0.31 mm, 0.26 mm, 0.24 mm, 0.21 mm, or 0.18 mm, respectively. Accordingly, tissue penetrators can have an outer diameter of up to 5 mm, such as up to 4.5 mm, up to 4 mm, up to 3.5 mm, up to 3 mm, up to 2.5 mm, up to 2 mm, up to 1.5 mm, up to 1 mm, or up to 0.5 mm. Tissue penetrator lengths (as measured from a distal tip to a proximal end that is attached or attachable to a support structure) can be less than 20 mm, less than 15 mm, less than 10 mm, less than 5 mm, less than 1 mm, or less than 0.5 mm. Tissue penetrator lengths can be at least 0.1 mm, at least 0.5 mm, at least 1 mm, at least 5 mm, or at least 10 mm.

[0083] The size of the tissue penetrator and number and size of cavities of the tissue penetrator can be selected to achieve a total cavity volume that provides for a desired total volume of payload. For example, the tissue penetrator can be configured for a total payload volume of at least 0.5 mm³, at least 1 mm³, at least 1.5 mm³, at least 2 mm³, at least 2.5 mm³, at least 3 mm³, at least 3.5 mm³, at least 4 mm³, at least 4.5 mm³, or at least 5 mm³. The tissue penetrator can be configured for a total payload volume of no more than 10 mm³, no more than 8 mm³, no more than 6 mm³, or no more than 4 mm³.

[0084] The cavities of tissue penetrators can be configured to provide a total payload-to-tissue contact area desired for a given application. The total payload-to-tissue contact area can be tuned to achieve a desired API release profile. Total payload-to-tissue contact area can be at least 1 mm², at least 5 mm², at least 10 mm², at least 15 mm², at least 20 mm², at least 30 mm², or at least 50 mm². Total payload-to-tissue contact area can be at most 100 mm², at most 50 mm², at most 30 mm², at most 20 mm², or at most 10 mm².

[0085] According to various embodiments, tissue penetrators are made using one or more additive manufacturing processes. For example, with reference to FIG. 5, one or more tissue penetrators 500 can be built up on a substrate 550 using a 3D printing system 580. Tissue penetrators 500 can be any of the tissue penetrators described herein, including anchoring tissue penetrator 104-A, non-anchoring tissue penetrator 104-B, and/or anchoring tissue penetrator 300. Substrate 550 can be any substrate described herein, including substrate 102 of FIG. 1. Suitable 3D printing systems can include stereolithography, material jetting systems, binder jet systems, and powder bed fusion systems. Additive manufacturing can enable the manufacturing of drug delivery devices having complex configurations that would be unachievable or impractical using other manufacturing techniques, such as subtractive manufacturing techniques or molding techniques. For example, the drug delivery device 100 of FIG. 1 can be made using additive manufacturing to build the tissue penetrators 104 directly onto the substrate 102. Additive manufacturing can be used to form different types of tissue penetrators onto the same substrate 102, such forming as anchoring tissue penetrators 104-A and non-anchoring tissue penetrators 104-B onto substrate 102.

[0086] Additionally, additive manufacturing can enable complex configurations of tissue penetrators. For example, additive manufacturing can be used to make tissue penetrator 300 of FIG. 3 as a single piece, which enables tissue penetrator 300 to be made smaller than would be achievable or practical if made as multiple pieces. Additionally or alternatively, additive manufacturing can be used to make different portions of tissue penetrator 300 out of multiple different materials. For example, hinge 310 of tissue penetrator 300 of FIG. 3 can be made from a weaker material than the extender so that the extender 308 bends at the hinge 310 without having to form the hinge 310 with a reduced thickness.

[0087] As illustrated in FIG. 5, cavities 502 of one or more tissue penetrators can be formed by the additive manufacturing process, which can allow for the formation of a much greater range of shapes and sizes of cavities than would be achievable or practical using other manufacturing techniques, such as subtractive manufacturing techniques or molding techniques. For example, undercut features, cavities that are interconnected beneath the surface of the tissue penetrator, and/or microfluidic channels are features that may be formed in the tissue penetrators using additive manufacturing that may not be possible using other manufacturing techniques.

[0088] In some embodiments, the payload is formed into the cavities during the additive manufacturing process. FIG. 6 illustrates an example of the 3D printing of a tissue penetrator 600 in which a payload 604 is 3D printed into the cavities 602 simultaneously with the formation of the cavities 602. 3D printing of payloads can allow for different types of payloads to be deposited in different cavities of the same tissue penetrator. For example, payload 604 can be 3D printed into a first set of cavities and a different type of payload 606 can be 3D printed into a second set of cavities 608.

[0089] As noted above, an anchoring tissue penetrator, such as anchoring tissue penetrator 104-A of FIG. 1 and anchoring tissue penetrator 300 of FIG. 3 can extend from a substrate for anchoring the substrate to the tissue. Alternatively, an anchoring tissue penetrator can be attached to or configured for attachment to other types of structures of drug delivery devices, such as an intraorgan drug delivery device or an orthopedic implant. FIG. 7 illustrates an example of an oral delivery device 700 that includes at least one anchoring tissue penetrator 702 for delivering one or more APIs to tissue 760 of the digestive tract, such as to the stomach lining. The oral delivery device 700 can include a main body 750 to which the tissue penetrator 702 is connected. The tissue penetrator 702 can be an anchoring tissue penetrator that includes one or more anchoring feature 754, such as any of the anchoring tissue penetrators described herein. The main body 750 can be configured for oral administration and to be conveyed by the digestive tract to a desired location where the tissue penetrator is forced into the tissue. In some embodiments, the main body 750 includes a mechanical actuator 752 that forces the tissue penetrator 702 into the tissue — for example, driven by a spring positioned within main body 750. In some embodiments, the tissue penetrator 702 is stored within the main body 750 and deployed at a desired time or upon reaching a desired location. For example, the main body 750 may include a dissolvable catch that when dissolved via interaction with stomach acid releases an actuator that deploys one or more tissue penetrators. The tissue penetrator 702 is configured to anchor the device 700 to the tissue so that it does not fall out as the one or more APIs are absorbing into the tissue. The tissue penetrator 702 may be configured to dissolve over a period of time.

[0090] FIG. 8 illustrates an example of a microneedle device 800 that includes a plurality of tissue penetrators 802 that extend from a substrate 850 for embedding into tissue 860. One or more of the tissue penetrators 802 may be an anchoring tissue penetrator that includes one or more anchoring features 852, according to the principles described herein. The microneedle device 800 can be or include, for example, a patch, an orthopedic plate, or a hydrogel. The device 800 can be, for example, a patch that is pressed onto a patient’s skin to deliver one or more API’s loaded in the plurality of tissue penetrators beneath the skin surface. The patch can be manually removed after a sufficient period of time has passed for the one or more APIs to be absorbed into the tissue.

[0091] According to various embodiments, a tissue penetrator according to the principles described herein is incorporated into a surgical staple, such as incorporated into or forming the penetrating ends of the surgical staple. The tissue penetrator may be configured to carry an API designed to enhance wound closure and healing. The tissue penetrator may be loaded to a device (e.g., a handheld device) that forces the tissue penetrator into tissue, such as via spring action. For example, a user may position a delivery end of the device at a desired location on a patient and may actuate the device (such as via a button push or trigger pull) and the device may force the tissue penetrator into the tissue to a desired depth.

[0092] The tissue penetrator could be (or could be incorporated into) an implantable rod for oncology treatment. The tissue penetrator could be (or could be incorporated into) orthopedic screws, femoral nails, and/or tendon anchors.

[0093] In some embodiments, tissue penetrator can be made of (or include) a metal, a ceramic material, or a polymeric material. The tissue penetrator material can be (or include) silicon or a metal or metal alloy such as stainless steel, titanium, magnesium allows, or a nickel titanium alloy. Exemplary types of medical grade polymeric materials include polycarbonate, liquid crystalline polymer (LCP), polyether ether ketone (PEEK), cyclic olefin copolymer (COC), and polybutylene terephthalate (PBT).

[0094] In some embodiments, the tissue penetrator material can be (or include) a biodegradable polymeric material. Exemplary types of medical grade biodegradable materials include polylactic acid (PLA), polyglycolic acid (PGA), PGA and PLA copolymer, and polyester-amide polymer (PEA).

[0095] In some embodiments, the tissue penetrator material can be (or include) an absorbable polyurethane, polycaprolactone (PCL), polydioxanone (PDO), polypropylene fumarate (PPF), poly(trimethylene carbonate) (PTMC), combinations thereof, and copolymers thereof with PLA and/or PGA.

[0096] In some embodiments, the tissue penetrator material can be (or include) photocurable resins composed of (meth)acrylate terminated absorbable polyester oligomers.

[0097] In some embodiments, the tissue penetrator or a portion thereof can be made from a dissolvable or degradable material. A dissolvable or degradable material can be any solid material that dissolves or degrades during use. For example, a tissue penetrator may be made to dissolve or degrade sufficiently in the tissue into which it is embedded. In some embodiments, the dissolvable or degradable material is selected from a carbohydrate or a sugar. In some embodiments, the dissolvable or degradable material is polyvinyl pyrrolidone (PVP). In some embodiments, the dissolvable or degradable material is selected from the group consisting of hyaluronic acid, carboxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinyl alcohol, sucrose, glucose, dextran, trehalose, maltodextrin, and any combination thereof.

[0098] Although tissue penetrating devices are described above for delivering an API into tissue, tissue penetrating devices can be configured with a plurality of cavities, according to the principles described herein, for taking samples from tissue. For example, a tissue penetrating device with unfilled cavities can insert into tissue, and cells, fluid, and/or other substance present in the tissue may migrate into the cavities. The tissue penetrating device can then be extracted from the tissue and the sample used, such as for diagnostic purposes. An anchoring tissue penetrator can anchor to the tissue as the samples are taken, either by the anchoring tissue penetrator itself (e g., absorbing the samples into one or more cavities) or by other tissue penetrators that are kept in place vie the anchoring tissue penetrator.

[0099] In some embodiments, the tissue penetrator or a portion thereof may include an imaging agent for enabling visualization of the tissue penetrator by an imaging system, which can be useful for confirming placement of the tissue penetrator in applications in which the tissue penetrator penetrates tissue within the body. The imaging agent can be, for example, a contrast agent that can be detecting by a fluoroscopic imaging system. In some embodiments, the imaging agent is a component of a material that forms at least a portion of the body 104 of tissue penetrator 100 of FIG. 1A. For example, the imaging agent may be a component of a 3D printing material used to 3D print the tissue penetrator. Additionally, or alternatively, the imaging agent can be loaded into one or more cavities of the tissue penetrator. For example, the imaging agent can be loaded into a set of one or more cavities and payload with one or more APIs can be loaded into a different set of one or more cavities, which can be done using a 3D printing process.

[0100] The foregoing description, for the purpose of explanation, has been described with reference to specific embodiments. However, the illustrative discussions above are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations are possible in view of the above teachings. The embodiments were chosen and described in order to best explain the principles of the techniques and their practical applications. Others skilled in the art are thereby enabled to best utilize the techniques and various embodiments with various modifications as are suited to the particular use contemplated.

[0101] Although the disclosure and examples have been fully described with reference to the accompanying figures, it is to be noted that various changes and modifications will become apparent to those skilled in the art. Such changes and modifications are to be understood as being included within the scope of the disclosure and examples as defined by the claims. Finally, the entire disclosure of the patents and publications referred to in this application are hereby incorporated herein by reference. 1

Claims

1. A drug delivery device comprising: a substrate; a plurality of tissue penetrating members positioned on the substrate and configured to embed into tissue, wherein at least one of the plurality of tissue penetrating members is configured to anchor the drug delivery device to the tissue; and at least one payload comprising at least one API loaded into at least one of the substrate and the plurality of tissue penetrating members for absorbing into the tissue when the at least one tissue penetrating member is embedded in the tissue.

2. The drug delivery device of claim 1, wherein the at least one of the plurality of tissue penetrating members comprises at least one barb for preventing pullout of the at least one of the plurality of tissue penetrating members.

3. The drug delivery device of claim 1 or claim 2, wherein the at least one of the plurality of tissue penetrating members comprises a curved tissue penetrating end for retaining the at least one of the plurality of tissue penetrating members in the tissue.

4. The drug delivery device of any of the preceding claims, wherein the substrate comprises a patch, a plate, a mesh, or a hydrogel.

5. The drug delivery device of any of the preceding claims, wherein a first set of the plurality of tissue penetrating members are configured for anchoring the drug delivery device to the tissue and a second set of the plurality of tissue penetrating members are configured to hold at least a portion of the at least one payload.

6. The drug delivery device of any of the preceding claims, wherein the plurality of tissue penetrating members are 3D printed onto the substrate using stereolithography or material jetting.

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

8. A method of delivering a drug to tissue, the method comprising: embedding a plurality of tissue penetrating members of a drug delivery device into the tissue, the plurality of tissue penetrating members positioned on a substrate; anchoring the drug delivery device into the tissue via at least one of the plurality of tissue penetrating members; and releasing at least one API that is loaded into at least one of the substrate and the plurality of tissue penetrating members into the tissue as the drug delivery device is anchored in the tissue.

9. The method of claim 8, wherein the at least one of the plurality of tissue penetrating members comprises at least one barb for preventing pullout of the at least one of the plurality of tissue penetrating members.

10. The method of claim 8 or claim 9, wherein the at least one of the plurality of tissue penetrating members comprises a curved tissue penetrating end for retaining the at least one of the plurality of tissue penetrating members in the tissue.

11. The method of any of claims 8-10, wherein the substrate comprises a patch, a plate, a mesh, or a hydrogel.

12. The method of any of claims 8-11, comprising anchoring the drug delivery device to the tissue by a first set of the plurality of tissue penetrating members and releasing the at least one API from a second set of the plurality of tissue penetrating members.

13. The method of any of claims 8-12, wherein the plurality of tissue penetrating were 3D printed onto the substrate using stereolithography or material jetting.

14. The method of any of claims 8-13, wherein the at least one of the plurality of tissue penetrating members has an outer diameter of up to 2 millimeters.

15. A method of making a drug delivery device, the method comprising: 3D printing a plurality of tissue penetrating members onto a substrate, the plurality of tissue penetrating members configured to embed into tissue, wherein at least one of the plurality of tissue penetrating members is configured to anchor the substrate to the tissue; and loading at least one of the substrate and the plurality of tissue penetrating members with a payload that comprises at least one API for absorbing into the tissue when the at least one tissue penetrating member is embedded in the tissue.

16. The method of claim 15, wherein the at least one of the plurality of tissue penetrating members comprises at least one barb for preventing pullout of the at least one of the plurality of tissue penetrating members.

17. The method of claim 15 or claim 16, wherein the at least one of the plurality of tissue penetrating members comprises a curved tissue penetrating end for retaining the at least one of the plurality of tissue penetrating members in the tissue.

18. The method of any of claims 15-17, wherein the substrate comprises a patch, a plate, a mesh, or a hydrogel.

19. The method of any of claims 15-18, wherein a first set of the plurality of tissue penetrating members are configured for anchoring the drug delivery device to the tissue and a second set of the plurality of tissue penetrating members are configured to hold at least a portion of the at least one payload.

20. The method of any of claims 15-19, wherein the plurality of tissue penetrating members are 3D printed onto the substrate using stereolithography or material jetting.

21. The method of any of claims 15-20, wherein the at least one of the plurality of tissue penetrating members has an outer diameter of up to 2 millimeters.

22. A drug delivery device for attaching to tissue comprising: at least one tissue penetrating member configured to embed into tissue, the at least one printed tissue penetrating member comprising: a main body that comprises a distal end for piercing the tissue, and at least one extender that is connected to the main body, wherein the at least one extender is configured to move relative to the main body from a retracted position to an extended position, wherein when the at least one tissue penetrating member is embedded in the tissue and the at least one extender is in the extended position, the at least one extender anchors the at least one tissue penetrating member in the tissue.

23. The drug delivery device of claim 22, wherein the main body and the at least one extender are 3D printed as a single piece.

24. The drug delivery device of claim 23, wherein the main body and at least one extender are 3D printed using at least one of stereolithography (SL) and material jetting (MJ).

25. The drug delivery device of any of claims 21-24, wherein the at least one extender is connected to the main body by a living hinge.

26. The drug delivery device of claim 25, wherein the living hinge and the at least one extender are formed of the same material.

27. The drug delivery device of claim 25 or claim 26, wherein the living hinge and the at least one extender are formed of different materials.

28. The drug delivery device of any of claims 22-27, wherein the at least one extender is configured to retract as the at least one extender moves past an outer surface of the tissue during insertion of the at least one tissue penetrating member into the tissue and is configured to extend after the at least one extender has moved past an outer surface of the tissue.

29. The drug delivery device of any of claims 22-28, wherein the at least one extender is connected to a collar that is movably mounted to the main body, and wherein movement of the collar toward the distal end moves the at least one extender to the extended position.

30. The drug delivery device of claim 29, wherein the collar is configured to move in response to a force that exceeds an insertion force threshold such that a force applied to the collar that is less than the insertion force threshold can cause insertion of the at least one tissue penetrating member into the tissue without causing movement of the at least one extender to the extended position and a force applied to the collar that is higher than the insertion force threshold can cause the at least one extender to move to the extended position.

31. The drug delivery device of any of claims 22-30, wherein the at least one tissue penetrating member has an outer diameter of up to 2 millimeters.

32. A method of delivering a drug to tissue, the method comprising: inserting at least a portion of at least one tissue penetrating member of a drug delivery device into the tissue; moving at least one extender of the at least one tissue penetrating member while the at least one extender is located within the tissue from a retracted position to an extended position to anchor the drug delivery device in the tissue; and releasing at least one API loaded into the drug delivery device into the tissue as the drug delivery device is anchored in the tissue.

33. The method of claim 32, wherein the at least one extender is 3D printed as a single piece with a main body of the at least one tissue penetrating member.

34. The method of claim 33, wherein the main body and at least one extender are 3D printed using at least one of stereolithography (SL) and material jetting (MJ).

35. The method of any of claims 32-34, wherein the at least one extender is connected to a main body by a living hinge.

36. The method of claim 35, wherein the living hinge and the at least one extender are formed of the same material.

37. The method of claim 35 or claim 36, wherein the living hinge and the at least one extender are formed of different materials.

38. The method of any of claims 32-37, wherein the at least one extender retracts as the at least one extender moves past an outer surface of the tissue during insertion of the at least one tissue penetrating member into the tissue and extends after the at least one extender has moved past an outer surface of the tissue.

39. The method of any of claims 32-38, wherein the at least one extender is connected to a collar that is movably mounted to a main body, and wherein moving the at least one extender from a retracted position to an extended position to anchor the drug delivery device in the tissue comprises moving the collar toward a distal end of the at least one tissue penetrating member to move the at least one extender to the extended position.

40. The method of claim 39, wherein inserting the at least a portion of at least one tissue penetrating member of a drug delivery device into the tissue comprises applying an insertion force to the collar to cause insertion of the at least one tissue penetrating member into the tissue without causing movement of the at least one extender to the extended position, and wherein a force applied to the collar to move the at least one extender to the extended position exceeds the insertion force applied to the collar.

41. The method of any of claims 32-40, wherein the at least one tissue penetrating member has an outer diameter of up to 2 millimeters.

42. A drug delivery device for targeting unhealthy tissue that has lower strength than healthy tissue of the same type, the device comprising: at least one tissue penetrating member configured to penetrate the unhealthy tissue when a penetration force is applied to the at least one tissue penetrator and fail to penetrate the healthy tissue when the penetration force is applied to the at least one tissue penetrator.

43. A drug delivery device for targeting unhealthy tissue that has higher strength than healthy tissue of the same type, the device comprising: at least one tissue penetrating member configured to penetrate into the healthy tissue and the unhealthy tissue and comprising one or more anchors that is configured to anchor the at least one tissue penetrating member to the unhealthy tissue but fail to anchor the at least one tissue penetrating member to the healthy tissue.