SWALLOWABLE DEVICE FOR DRUG DELIVERY IN THE INTESTINAL TRACT - Patent application

Abstract

The delivery device may include a capsule housing, at least one tissue-piercing member within a sealed compartment within the capsule housing, the at least one tissue-piercing member configured to release a payload, and an actuator within the capsule housing and at least partially outside the sealed compartment, the actuator configured to advance the at least one tissue-piercing member out of the sealed compartment.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Patent Application No. 62 / 960,977, filed January 14, 2020, which is incorporated herein by reference in its entirety.

[0002] The present invention relates generally to the field of drug delivery devices. [Background technology]

[0003] Medical treatment of many conditions involves the use of drugs that are traditionally administered to patients in a variety of ways, such as orally or by injection (e.g., subcutaneous injection). However, these drug delivery modes have drawbacks. For example, with traditional oral administration, patients may experience stomach irritation or other discomfort, and / or the drug may undergo undesirable degradation as a result of digestion in the gastrointestinal tract. Additionally, some therapeutic agents (e.g., macromolecules) cannot be delivered orally. As another example, injections are painful and inconvenient, often affecting patient compliance and quality of life. These problems are magnified in the case of chronic medical conditions that require sustained or repeated administration of drugs. Thus, new and improved methods and devices for delivering drugs to patients are needed. Summary of the Invention

[0004] In some variations, the delivery device includes a capsule housing, at least one tissue-piercing member within a sealed compartment within the capsule housing, and an actuator within the capsule housing at least partially outside the sealed compartment. The at least one tissue-piercing member may be configured to release a payload or other therapeutic agent, such as a drug. The actuator may be configured to advance the at least one tissue-piercing member out of the sealed compartment. For example, in some variations, the sealed compartment may include one or more seals, and the actuator may be configured to break the at least one seal and / or advance the at least one tissue-piercing member through the at least one seal.

[0005] The sealed compartment may be configured to protect the tissue-piercing member from degradation (e.g., from the environment of the gastrointestinal tract) until advanced into the tissue, thereby substantially reducing or eliminating the risk of premature release of the drug where the drug is not readily absorbed. Thus, the sealed compartment may help maintain the therapeutic effect of the dose of drug provided in the drug delivery device. [Brief description of the drawings]

[0006] [Figure 1A] 1 shows a schematic diagram of an example of a variation of a swallowable drug delivery device. [Figure 1B] 1 shows a schematic diagram of a tissue penetrating member within a sealed compartment. [Figure 1C] FIG. 1C shows a schematic diagram of the tissue penetrating member shown in FIG. 1B being advanced out of the sealed compartment. [Figure 2A] 1 is a schematic diagram of an example of a variation of a swallowable drug delivery device. [Figure 2B] 1 shows a schematic diagram of multiple tissue penetrating members within a sealed compartment. [Diagram 3] 13A-13C show schematic diagrams of one example of a variation of a tissue penetrating member within a sealed compartment. [Figure 4A-4C] 13A-13C show schematic diagrams of variations of tissue penetrating members configured to release drugs. [Figure 5A-5B] 13A-13C show schematic views of the distal end of a variation of a tissue penetrating member. [Figure 6A] 1 shows a schematic diagram of a drug delivery device including an example of a modified actuator. [Figure 6B] FIG. 6B shows a schematic diagram of the actuator shown in FIG. 6A after removing the capsule housing. [Figure 6C] FIG. 6C depicts a schematic diagram of the actuator shown in FIG. 6B in an expanded configuration for advancing one or more tissue penetrating members. [Figure 7A] 1 shows a schematic diagram of a drug delivery device including an example of a modified actuator. [Figure 7B] FIG. 7B shows a schematic diagram of the actuator shown in FIG. 7A after removing the capsule housing. [Figure 7C] FIG. 7C depicts a schematic diagram of the actuator shown in FIG. 7B in an expanded configuration for advancing one or more tissue penetrating members. [Figure 8A] 1 shows a schematic diagram of a drug delivery device including an example of a modified actuator. [Figure 8B] FIG. 8B depicts a schematic diagram of the actuator shown in FIG. 8A in an expanded configuration for advancing one or more tissue penetrating members. [Figure 9A] 1 shows a schematic diagram of a drug delivery device including an example of a modified actuator. [Figure 9B] FIG. 9B shows a schematic diagram of the actuator shown in FIG. 9A after removing the capsule housing. [Figure 9C] FIG. 9C depicts a schematic diagram of the actuator shown in FIG. 9B in an expanded configuration for advancing one or more tissue penetrating members. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007] Non-limiting examples of various aspects and variations of the present invention are described herein and illustrated in the accompanying drawings.

[0008] As used in this disclosure, the terms "eg," "such as," "for example," "examples of," and "by way of example" indicate that a list of one or more non-limiting examples is preceded or followed, and it is to be understood that other examples not listed are within the scope of the disclosure.

[0009] As used herein, the terms "substantially" and "about" are used to describe and convey small variations. For example, when used in conjunction with a numerical value, these terms can refer to a variation range of ±10% or less of that numerical value, such as ±5% or less, ±4% or less, ±3% or less, ±2% or less, ±1% or less, ±0.5% or less, ±0.1% or less, or ±0.05% or less.

[0010] As used herein, a range of numerical values ​​includes any number within the range, or any subrange where the minimum and maximum numbers within the subrange are within the range. Thus, for example, "<9" may refer to any number less than 9, or to a subrange of numerical values ​​where the minimum value of the subrange is equal to or greater than zero, and the maximum value of the subrange is less than 9.

[0011] The delivery device described herein delivers a payload to a site, such as an internal site (e.g., within the body of a human or other animal). The payload can be or include one or more pharmaceutical preparations, electronic devices, or a combination of the above. The pharmaceutical preparations can be in powder form, or in a compact or consolidated form, such as a tablet or micro-tablet. The delivery device can include one or more pharmaceutical preparations. The pharmaceutical preparations can include one or more agents. A wide range of agents can be used. For example, the agent can be or include any pharmacologically active agent (e.g., antibiotics, NSAIDs, angiogenesis inhibitors, neuroprotective agents, chemotherapeutic agents), DNA or siRNA transcripts (e.g., for modifying a genetic abnormality, condition, or disorder), cells (e.g., produced by or from an organism, or including components of an organism), cytotoxic agents, diagnostic agents (e.g., sensing agents, contrast agents, radionuclides, fluorescent moieties, luminescent moieties, magnetic moieties), prophylactic agents (e.g., vaccines), dietary supplements (e.g., vitamins, minerals, herbal supplements), delivery enhancers, retardants, excipients, another substance, or any combination of two or more of the foregoing. The agent can be suitable for introduction into biological tissue. For convenience of nomenclature, the delivery device may be labeled herein as a "drug delivery" device, but more generally, the delivery device may deliver a payload that may include one or more pharmaceutical agents and / or electronic devices as described above. Additionally, for convenience of nomenclature, the payload may be referred to herein as a "drug," however, the payload may be or include one or more pharmaceutical agents, electronic devices, or combinations of the foregoing.

[0012] As described in further detail herein, drug delivery devices and methods may utilize a swallowable device to deliver a payload to various locations in the body. In some variations, the drug delivery device may be a swallowable device configured to deliver one or more therapeutic agents to the gastrointestinal tract. As described in further detail below, the drug delivery device may include a capsule housing, at least one tissue penetrating member configured to release a payload, and an actuator within the capsule housing and configured to advance the tissue penetrating member into tissue where the payload may be released. For example, the tissue penetrating member may include a biodegradable material that releases the drug when the tissue penetrating member degrades.

[0013] In some variations, the tissue penetrating member may be in a sealed compartment within the capsule housing, and the actuator may be at least partially outside the sealed compartment and configured to advance the tissue penetrating member from the sealed compartment into nearby tissue. The sealed compartment may be configured to protect the tissue penetrating member from degradation (e.g., from the environment of the gastrointestinal tract) until it is advanced into the tissue. For example, the sealed compartment may be configured to protect the tissue penetrating member, thereby substantially reducing or eliminating the risk of premature release of the drug where the drug is not readily absorbed. Thus, such a sealed compartment for the tissue penetrating member may help maintain the therapeutic effect of a dose of the drug provided in the drug delivery device.

[0014] 1A-1C, a drug delivery device 100 may include a capsule housing 110, at least one tissue-piercing member 130 configured to release a drug 140 (or other payload 140) within a sealed compartment 120, and an actuator 150 within the capsule housing 110 at least partially outside the sealed compartment 120. The actuator 150 may be configured to advance the tissue-piercing member 130 from the sealed compartment 120 into tissue (T).

[0015] Once swallowed, the drug delivery device 100 may travel through the gastrointestinal tract and the capsule housing 110 may degrade as a result of the environment (e.g., pH) of the gastrointestinal tract. In some variations, the actuator 150 may prevent the advancement of the tissue penetrating member 130 until the capsule housing degrades (e.g., using one or more biodegradable restraining features described further below). For example, during or after the capsule housing degrades, the actuator may be exposed to environmental conditions, thereby actuating to advance the tissue penetrating member 130 into the intestinal wall. However, the sealed compartment 120 may protect the exposure of the tissue penetrating member 130 to the same environmental conditions until the actuator is fully actuated to advance the tissue penetrating member 130 into the tissue, e.g., to the point where the drug 140 is released. Thus, a drug delivery device with a sealed compartment 120 may reduce or prevent premature degradation of the tissue penetrating member 130 and release of the drug 140, e.g., helping to maintain the full therapeutic effect of the drug dose contained in the tissue penetrating member 130.

[0016] Capsule Housing In general, the capsule housing may be sized and shaped to be swallowed and enter the gastrointestinal tract. For example, as shown in FIG. 1A, the capsule housing may be spherical-cylindrical (e.g., cylindrical with hemispherical or otherwise rounded ends). However, the capsule housing may have any suitable shape, such as spherical or elliptical. The capsule housing may have rounded edges. This may help to avoid swallowing difficulties and / or damage to the gastrointestinal tract during the passage of the drug delivery device.

[0017] The capsule housing may include an internal volume for accommodating one or more other components of the drug delivery device, such as one or more sealed compartments, tissue-piercing members, and / or actuators. The capsule housing may have a capsule wall that defines the internal volume. In some variations, the internal volume may be substantially sealed (e.g., the capsule housing may completely enclose its contents). The capsule housing may include one or more openings (e.g., to allow passage of one or more tissue-piercing members) that may be temporarily covered with a dissolvable coating or other seal. Additionally, in some variations, the capsule housing may include one or more capsule walls that form one or more partitions of the internal capsule volume, thereby dividing the internal capsule volume in any suitable manner.

[0018] The capsule housing may include any suitable biodegradable material, such as one or more biodegradable polymers. The capsule housing may, for example, be formed from such biodegradable materials and / or may include a biodegradable coating. Examples of biodegradable polymers that may be suitable for use in the methods and devices described herein include, but are not limited to, hydroxypropylmethylcellulose (HPMC), lactide, glycolide, lactic acid, glycolic acid, paradioxanone, trimethylene carbonate, caprolactone, and mixtures and copolymers thereof. In one or more embodiments, the capsule housing is formed of one or more layers of HPMC, and further, in some variations, the capsule housing may include an enteric coating that helps prevent the capsule housing from dissolving in the stomach before entering the intestine.

[0019] The capsule housing may be configured to disintegrate in whole or in part during passage through the gastrointestinal tract. For example, the capsule housing may disintegrate to expose at least a portion of its contents of the internal capsule volume. In some variations, the material of the capsule housing may be configured to disintegrate in an intestinal environment (e.g., the small intestine) having a pH of at least about 5.5. For example, the capsule housing may be formed from a material and / or may include a coating configured to disintegrate in an environment having a pH of at least 5.5, at least 6.0, at least 6.5, at least 7.0, at least 7.1, at least 7.2, at least 7.3, at least 7.4, at least 7.5, at least 7.6, at least 7.7, at least 7.8, at least 7.9, at least 8.0, etc. In some variations, the dimensions and material of the capsule housing may be selected such that the capsule housing (or a coating thereon) is configured to disintegrate in the gastrointestinal tract over a predetermined period of time, e.g., from about 4 hours to about 10 hours, from about 5 hours to about 9 hours, or from about 6 hours to about 8 hours. The predetermined period of time may be selected based, at least in part, on the desired location for payload delivery (e.g., stomach, small intestine, large intestine, etc.), the estimated rate of movement of the capsule housing through the gastrointestinal tract due to peristalsis, and / or other factors.

[0020] The capsule housing may be configured to dissolve in its entirety, and / or the capsule housing may be broken into smaller pieces (e.g., due to dissolvable joints or seams) to facilitate easier passage through the patient's gastrointestinal tract. In variations in which the capsule housing is broken into smaller pieces, the smaller pieces may be joined by seams in any suitable pattern (e.g., grids, rings, etc.). Such seams may include a biodegradable material and / or may be formed by prestressing or otherwise weakening portions of the capsule housing. Additionally, in variations in which the capsule housing includes one or more openings (e.g., for passage of one or more tissue penetrating members), the one or more openings may be covered by a dissolvable seal that includes a biodegradable material (e.g., a pH-controlled material similar to those described above).

[0021] The particular size and / or shape characteristics of the capsule housing may be selected based on the application (e.g., volume of drug to be delivered, size or age of the patient, etc.). For example, in some variations, the length of the capsule housing may range from about 0.25 inches to about 2 inches, from about 0.5 inches to about 1.5 inches, from about 0.75 inches to about 1.25 inches, etc. In some variations, the diameter of the capsule housing may range, for example, from about 0.1 inches to about 0.5 inches.

[0022] Sealed compartment In some variations, the drug delivery device may include one or more sealed compartments. The sealed compartments may, for example, function to temporarily protect at least one tissue-piercing member contained therein from environmental factors (e.g., the higher pH of the intestine) that may prematurely degrade the tissue-piercing member before it is advanced into the tissue for payload delivery. In other words, the sealed compartments may delay exposure of the tissue-piercing member to degradative conditions until it is advanced by the actuator into the intestinal wall or other tissue.

[0023] In some variations, the sealed compartment may include one or more seals coupled to the chamber, guide tube, or similar structure that includes at least one tissue penetrating member. The one or more seals may form a fluid-tight seal to substantially prevent fluid from entering the compartment. The sealed compartment may be breached at the appropriate time to allow the tissue penetrating member contained therein to exit the tissue sealed compartment to penetrate the tissue and deliver the payload. The sealed compartment may include mechanical seals that may be breached by mechanical processes (e.g., drilling, perforation, loosening, etc.) and / or chemical seals that may be breached by chemical processes (e.g., dissolution, other chemical degradation, etc.), as further described below.

[0024] 1B and 1C show an example of a variation of the sealed compartment 120 for the tissue penetrating member 130. As shown in FIG. 1B, the sealed compartment 120 may include a proximal seal 122 and / or a distal seal 124 at either end of the guide tube or chamber 125. The proximal seal 122 and / or the distal seal 124 may include a mechanical seal, such as a layer of foil or film of a biocompatible material that may be pierced to provide access into and / or out of the sealed compartment 120. For example, the proximal seal 122 and / or the distal seal 124 may include a foil seal made of aluminum or other suitable material that provides sufficient rigidity and penetrability. In one or more embodiments, the proximal seal 122 and / or the distal seal 124 is an aluminum foil about 10 micrometers to about 20 micrometers thick bonded with an ethylene vinyl acetate (EVA) or poly(ethylene vinyl acetate) (PEVA) thermal adhesive. In some variations, the material of one or more of the proximal seal 122, the distal seal 124, and / or the walls of the compartment 120 may be biodegradable. In some variations, other portions of the compartment 120 may include a biodegradable polymer, such as any of those described above with respect to the encapsulant.

[0025] As described in further detail below, the actuator 150 may include a drive member 152 or other suitable features arranged to cause breaching of the proximal seal 122 and / or the distal seal 124 when the actuator 150 is activated. The drive member 152 may operate similarly to a piston or plunger in the guide chamber 125 adjacent the sealed compartment 120. For example, as shown in FIG. 1C , the drive member of the actuator 150 may have a sharp tip and be triggered to pierce the proximal seal 122. After piercing the proximal seal 122, the drive member may then urge the tissue penetrating member 130 to pierce the distal seal 124, thereby advancing the tissue penetrating member 130 out of the sealed compartment 120. In some variations, one or both of the drive member 152 and the chamber adjacent to the sealed compartment 120 (and / or the sealed compartment 120) may include directional features (e.g., notches) to allow movement of the drive member 152 in one direction (e.g., a distal direction to advance the tissue-penetrating member 130) and resist movement of the drive member 152 in the opposite direction, thereby constraining the drive member 152 to move in a predetermined direction.

[0026] In some variations, the drug delivery device may include multiple sealed compartments for housing and protecting multiple tissue penetrating members. For example, FIGS. 2A and 2B show schematic diagrams of a drug delivery device 200 and an arrangement of multiple sealed compartments 220, respectively. Features of the drug delivery device 200 are numbered similarly to those shown and described above with respect to the drug delivery device 100 shown in FIGS. 1A-1C. Although three sealed compartments are depicted for illustrative purposes, it should be understood that any suitable number of sealed compartments (such as 2, 4, 5, 6 or more) may be included in the drug delivery device. The multiple sealed compartments may be arranged in any suitable manner, such as in a column, ring or other perimeter, a cluster, a matrix of two or more rows and two or more columns, a corner-to-corner arrangement, or other arrangement.

[0027] The operation and function of the sealed compartments 220 may be generally similar to that shown and described above with respect to FIGS. 1A-1C. However, as shown in detail in FIG. 2B, the drug delivery device 200 may include multiple sealed compartments 220, each including a respective tissue-piercing member 230 including a payload 240. Additionally, the actuator 250 may include multiple drive members 252 or other suitable features, each configured to pierce the proximal seal 222 and advance the tissue-piercing member 230 out of (e.g., through the distal seal 224) a respective sealed compartment 220. Although the drive members 252 are shown in FIG. 2B as being simultaneously driven by a common actuator 250, it should be understood that some or all of the drive members 252 may be separately and individually actuated by respective actuators. In some variations, multiple actuators may be configured to be activated at different times such that the tissue-piercing member is advanced out of the sealed compartment in stages. Additionally, while the variation shown in FIG. 2B includes each tissue-piercing member 230 contained individually in a respective sealed compartment 220, it should be understood that in some variations, some or all of the multiple tissue-piercing members may share a sealed compartment 220.

[0028] In some variations, the sealed compartment may include one or more seals formed as a result of an engineered fit between a sealing feature and at least one surface of the sealed compartment (e.g., a wall of a guide tube or chamber). For example, FIG. 3 shows an example of an arrangement variation in which a sealed compartment 320 containing a tissue penetrating member 330 has a proximal seal 322 and a distal seal 324. The proximal seal 322 may be formed by an engineered fit between an outer surface of a drive member 352 of the actuator 350 and an inner surface of a wall of the sealed chamber 320. The outer diameter of the drive member 352 may be sufficiently oversized relative to the inner diameter of the compartment 320, for example, to form a sufficiently fluid-tight fit. However, the relative sizes of the drive member 352 and the compartment 320 may further be selected to allow the actuator force to overcome friction in the engineered fit and allow the actuator 350 to advance the tissue penetrating member 330 through the distal seal 324 and out of the sealed compartment 320.

[0029] Additionally or alternatively, the sealed compartment may include one or more seals that may dissolve or otherwise chemically degrade. For example, the sealed compartment may include a proximal seal and / or a distal seal (similar to those shown in FIG. 1B or FIG. 2B) that include a biodegradable material, such as a biodegradable polymer, including those described above with respect to the capsule housing. In these variations, instead of being pierced by an actuator or tissue penetrating member, the seal may dissolve as a result of the environmental conditions (e.g., pH) of the intestinal tract. Furthermore, in some variations, both chemical and mechanical processes may breach one or more seals of the sealed compartment. For example, a chemical degradation process may weaken a mechanical seal over time (e.g., a predetermined delay period) to make it easier for an actuator to penetrate the mechanical seal. As another example, the sealed compartment may include both at least one chemical seal and at least one mechanical seal (e.g., a chemical proximal seal and a mechanical distal seal).

[0030] In some variations, other forms of protection of the tissue-penetrating member from degradation conditions may additionally or alternatively be provided. For example, the sealed compartment wall, one or more seals, and / or the tissue-penetrating member itself may include a protective outer coating. Such a protective outer coating may be configured to dissolve or otherwise degrade over time when in the environmental conditions of the intestinal tract. Any of the above types of protection (e.g., mechanical seals, chemical seals, coatings, etc.) may be combined in any suitable manner to delay the release of the payload in the tissue-penetrating member until the tissue-penetrating member is advanced into the tissue for drug delivery.

[0031] Tissue penetrating member As described above, the drug delivery device may include one or more tissue-penetrating members (e.g., microneedles) configured to release a payload, such as a therapeutic agent. In some variations, the tissue-penetrating members may be hollow (e.g., may include a lumen or other depression) and include a payload, such as a drug. Alternatively, as described in more detail below, the tissue-penetrating members may be solid (e.g., may be formed at least in part from the drug itself). In variations in which the drug delivery device includes multiple tissue-penetrating members that include a drug, each of the tissue-penetrating members may include the same or similar drug, or one or more of the tissue-penetrating members may include different payloads. Additionally, in some variations in which the payload is a therapeutic agent, the tissue-penetrating members may include a preparation of multiple therapeutic agents combined.

[0032] In general, the tissue penetrating member may include a shaft and a tip suitable for penetrating tissue. Once placed in tissue, the tissue penetrating member may degrade due to conditions in the tissue, thereby releasing the payload (e.g., the tissue penetrating member degrades and dissolves to release the payload), and if the payload is a drug, the drug is absorbed into the bloodstream. In some variations, the tissue penetrating member may include one or more retention features, such as barbs, hooks, texture features (e.g., frictional bumps or rings, etc.), to help secure the tissue penetrating member to the tissue once placed. The retention features may be arranged around the outer surface of the tissue penetrating member, for example, in a ring, spiral, grid, or any suitable pattern.

[0033] In some variations, the tissue-penetrating member may include a biodegradable material so that it is dissolvable after penetrating tissue, etc. Like the capsule housing described above, in some variations, the tissue-penetrating member may include one or more biodegradable seams to allow the tissue-penetrating member to break into smaller pieces. The material of the tissue-penetrating member may be selected to provide suitable structural characteristics (e.g., stiffness and / or column strength) and / or based on degradation qualities (e.g., speed). For example, the tissue-penetrating member may include a biodegradable polymer such as polyethylene glycol (PEG) (e.g., injectable grade PEG). As another example, the tissue-penetrating member may additionally or alternatively include cellulose, or a sugar such as maltose.

[0034] For embodiments in which the payload includes a therapeutic agent, the tissue-penetrating member may include any suitable dose of the therapeutic agent. For example, in some variations, the tissue-penetrating member may include about 0.1 mg to about 10 mg, about 1 mg to about 8 mg, about 1 mg to about 5 mg, or about 1 mg to about 3 mg of a drug or other therapeutic agent. However, the specific amount of the therapeutic agent may be adjusted based on the type of therapeutic agent, the number of drug delivery devices intended to be taken at any particular time, the characteristics of the patient (e.g., age, weight, sex, BMI, etc.), and the like. The therapeutic agent may be formulated to achieve a desired pharmacokinetic profile. For example, in one or more embodiments in which the therapeutic agent includes a basal insulin, the therapeutic agent has a formulation designed to achieve a half-life of at least 24 hours for the basal insulin in the formulation.

[0035] As shown in Figures 4A and 4B, the biodegradable material 410 may be included with the drug 420 within the tissue penetrating member in a variety of ways. For example, as shown in Figure 4A, the tissue penetrating member 400a may include a biodegradable material 410 forming a member body having a sharp penetrating tip and a lumen or cavity for receiving the drug 420. The member body may include a biodegradable polymer as described above, which may be formed into the member body, for example, by molding or other suitable techniques. The drug 420 may be, for example, in a solid form (e.g., a powder, a tablet, a cylindrical slug, or a volume of other suitable shape, etc.) configured to reside in the cavity of the member body. For example, a powder may be poured and / or packed into the cavity of the tissue penetrating member. As another example, a solid form of the drug may be formed separately and then inserted into the cavity of the tissue penetrating member. In other variations, the drug may be in a semi-liquid, liquid, or other fluid form that is poured into the cavity of the tissue penetrating member.

[0036] The drug 420 may further be contained in a recess in the member body with a dissolvable or otherwise degradable seal 430 (e.g., heat seal, chemical seal, foil seal, etc.) Formation of the tissue penetrating member may be accomplished using suitable polymer and / or pharmaceutical manufacturing techniques (e.g., molding, etc.).

[0037] As another example, as shown in FIG. 4B, tissue-piercing member 400b may include a biodegradable material 410 formed into a member body with a sharp penetrating tip, and a coating on the member body including a drug 420. Drug 420 may be deposited, for example, as a conformal coating on the member body (e.g., using dipping, spraying, or other suitable process). The drug coating may be present around the entire member body, or only a portion of the tissue-piercing member. In some variations, the drug coating may be substantially uniform in thickness or may vary in thickness. The thickness may also be selected depending, for example, on the desired dose of drug and / or the surface area of ​​the tissue-piercing member exposed for drug absorption.

[0038] In some variations, the tissue-piercing member may include a drug that is not combined with a biodegradable material but is fabricated into the shape of the tissue-piercing member. For example, as shown in FIG. 4C, tissue-piercing member 400c may include a drug 420 that is formed into the member body with a sharp penetrating tip, such as by shaving, molding, and / or any suitable forming technique.

[0039] It should also be understood that a drug (or drugs) may be included in the tissue-penetrating member in a combination of ways. Any two or more aspects of the above variations of the tissue-penetrating member may be combined. For example, the tissue-penetrating member may include a depression including a first drug (e.g., as shown in FIG. 4A) in addition to a drug coating including a second drug (e.g., as shown in FIG. 4B). As another example, the tissue-penetrating member may be formed from a first drug (e.g., as shown in FIG. 4C) and include a depression including a second drug (e.g., as shown in FIG. 4A). As another example, the tissue-penetrating member may be formed from a first drug (e.g., as shown in FIG. 4C) and include a coating including a second drug (e.g., as shown in FIG. 4B). As yet another example, the tissue-penetrating member may be formed from a first drug (e.g., as shown in FIG. 4C), include a depression including a second drug (e.g., as shown in FIG. 4A), and include a coating including a third drug (e.g., as shown in FIG. 4B). Alternatively or additionally to any of the foregoing examples, the tissue penetrating member may include multiple drugs, such as two or more tablets each containing a drug formulation.

[0040] Additionally, in some variations, the penetrating end of the tissue-piercing member may include a tip augmenting feature. The tip augmenting feature may increase the piercing ability of the tissue-piercing member, for example, by increasing the sharpness of the tissue-piercing member, increasing stiffness, etc. For example, as shown in Figures 5A and 5B, the tissue-piercing member may include a tip augmenting feature 540 that provides a sharper or pointed tip for more easily penetrating tissue. Such a tip augmenting feature 540 may be made from a relatively stiff material, such as a metal (e.g., magnesium), which may be better formed into and / or retain its sharp shape compared to a tip formed solely from a biodegradable polymer, for example, due to different material properties.

[0041] The tip augmenting feature 540 may be coupled to the distal end of the tissue penetrating member. For example, as shown in FIG. 5A, the tip augmenting feature 540 may be at least partially embedded in the distal end of the tissue penetrating member. In some variations, the tip augmenting feature 540 may be formed (e.g., molded) separately and inserted into the distal end of the tissue penetrating member. Alternatively, in some variations, the tip augmenting feature 540 may be formed by overmolding (co-molding) the biodegradable material 510 onto the tip augmenting feature 540. In general, retention of the tip augmenting feature 540 within the distal end of the tissue penetrating member may be improved by friction or texture features, interlocking features, an interference fit, or the like.

[0042] As another example, as shown in Figure 5B, a tip augmenting feature 540 may additionally or alternatively be coupled to an outer surface of the distal end of the tissue-piercing member, such as a spike cap. Similar to the variation described above with respect to Figure 5A, the tip augmenting feature 540 shown in Figure 5B may be formed separately and subsequently coupled to the distal end of the tissue-piercing member.

[0043] It should be understood that although the variations of the tissue-piercing members shown in Figures 4A-4C and Figures 5A and 5B include a shaft and a single pointed tip, other variations of the tissue-piercing members may have other suitable shapes (e.g., multiple unevenly angled prongs or spikes, such as a quill or lamp shape).

[0044] Actuator As described above, the drug delivery device may include one or more actuators coupled to at least one tissue penetrating member. The one or more actuators may be configured to advance the at least one tissue penetrating member into tissue (e.g., an intestinal wall). For example, as described above with respect to Figures 1B and 1C, the actuator may be configured to advance the tissue penetrating member out of the sealed compartment. In some variations, the actuator may be triggered to transition from a first state in which the actuator is prevented from actuating the tissue penetrating member to a second state in which the actuator actuates the tissue penetrating member.

[0045] For example, in some variations, the first actuator state may be maintained by one or more restraints or other suitable release features. In other words, the restraint may substantially prevent the actuator from advancing the tissue-penetrating member, and in the absence of the restraint, the actuator may transition to the second state or activate the actuator to advance the tissue-penetrating member. The restraint may include, for example, a biodegradable material that degrades in an intestinal environment, such that after a predetermined period of time, the restraint is removed, thereby allowing the actuator to advance the tissue-penetrating member. For example, the restraint may be configured to degrade in an intestinal environment (e.g., the small intestine) having a pH of at least about 5.5. For example, at least a portion of the restraint may be configured to degrade in an environment having a pH of at least 5.5, at least 6.0, at least 6.5, at least 7.0, at least 7.1, at least 7.2, at least 7.3, at least 7.4, at least 7.5, at least 7.6, at least 7.7, at least 7.8, at least 7.9, at least 8.0, etc.

[0046] In some variations, the actuator may include an expandable device, where expansion of the expandable device is configured to actuate the tissue penetrating member. For example, the actuator may include a drive member and an expandable device configured to actuate the drive member to advance the tissue penetrating member. A portion of the expandable device and / or the actuator may include a biodegradable material. For example, the expandable device, the drive member, and / or other portions of the actuator may include a biodegradable material with sufficient stiffness, such as cellulose and poly(vinyl alcohol) (PVA).

[0047] For example, Figures 6A-6C illustrate the operation of an actuator including at least one drive member and at least one expandable device configured to actuate the drive member. As shown in Figure 6A, the drug delivery device 600 can include a capsule housing 610 with an actuator including an expandable device 654. The expandable device 654 includes expansion struts similar to a scissor jack or lift jack mechanism. For example, the expansion struts can be joined at a pivot point 656 that can include a passive hinge and / or a spring (e.g., a torsion spring) to help actuate the expansion of the expandable device 654.

[0048] As shown in FIG. 6A, the expandable device 654 is restrained in the loaded, collapsed configuration by one or more restraints 660 (two restraints 660 are shown in FIG. 6A as an example). The restraints 660 may include, for example, bands, straps, etc. coupled to the expansion struts to hold the expandable device in the collapsed configuration. Although the restraints 660 are shown as coupled to the internal struts, it should be understood that the restraints may be coupled to or around any suitable portion of the expandable device (e.g., around the entire device) to restrain the expandable device 654 in the collapsed state. Additionally, the drug delivery device may include other variations of restraints including, for example, braces, clips, bags surrounding the expandable device, etc.

[0049] The restraint 660 may comprise a biodegradable material such that degradation of the restraint (e.g., in the gastrointestinal environment) may eventually cause release of the expandable device. For example, as shown in FIG. 6B, degradation of the capsule housing 610 may gradually dissolve exposing the restraint 660 (while the tissue penetrating member remains protected within the sealed compartment 620).

[0050] After the restraint 660 is sufficiently removed in the degradation process, the expandable device 654 may transition to its expanded state shown in FIG. 6C. Alternatively, in some variations, the restrained expandable device 654 may be expelled from the capsule housing 610, such as by a spring release triggered by environmental conditions. One or more tissue penetrating devices in one or more sealed compartments 620 are coupled to the expandable device 654 via the drive member 652 (e.g., with an additional torsion spring (not shown)), such that expansion of the expandable device 654 causes the drive member 652 to advance the tissue penetrating device out of the sealed compartment 620 (e.g., as described above). The tissue penetrating member may be advanced into the tissue where it may release a payload (e.g., a drug to the patient for a therapeutic effect). Following delivery of the tissue penetrating device to the tissue, at least some of the other components of the actuator of FIGS. 6a-6c may continue to dissolve and / or may be passed through the patient's gastrointestinal tract.

[0051] In some variations, multiple separate arrangements of tissue-piercing members may be coupled to an actuator (or multiple respective actuators). For example, the expandable device 754 in the drug delivery device 700 shown in FIG. 7A is similar to the expandable device 654 described above with respect to FIGS. 6A-6C, except that two chambers or sealed compartments 720 are coupled to the expandable device 754. As shown in FIG. 7A, for example, two sealed compartments 720 are coupled to both sides of the expandable device 754. After the capsule housing dissolves, the restraint 760 may be exposed and undergo degradation (while the sealed compartments 720 protect the tissue-piercing members contained therein), as shown in FIG. 7B. Alternatively, in some variations, the restrained expandable device 754 may be ejected from the capsule housing 710, such as by a spring release triggered by environmental conditions. Upon disassembly or other removal of the restraint 760, the expandable device 754 may expand, thereby compressing the sealed compartment 720 in both directions, such as by torsional spring action of one or more torsion springs (e.g., one, two, three, or more torsion springs). Although two opposing sealed compartments 720 are shown in FIG. 7A, it should be understood that the expandable device may include three, four, or any suitable number of multiple sealed compartments that expand outward. A drive member actuated by the expandable device 754 and / or other actuators may advance the tissue-piercing member from the sealed compartment 720 into the tissue, as described above. Following delivery of the tissue-piercing device to the tissue, at least some of the other components of the actuator may continue to dissolve and / or may be passed through the patient's gastrointestinal tract.

[0052] Although the drug delivery device is shown with two sealed compartments 720 in Figures 7A, 7B and one sealed compartment 620 in Figures 6A-6C, additional sealed compartments 620 or 720 may be used.

[0053] Additionally, other variations of the expandable device may additionally or alternatively be included in the drug delivery device, and at least one sealed compartment containing one or more tissue penetrating members may be disposed on the expandable device in any suitable manner.

[0054] For example, in some variations, such as the drug delivery device 800, as shown in FIGS. 8A and 8B, the expandable device may include at least one inflatable device 854, such as a balloon. The inflatable device 854 may include a suitable polymer, such as, for example, PET, polyethylene, or polyimide. The inflatable device 854 may be disposed within the capsule housing 810 and configured to transition from a collapsed (or partially collapsed) state shown in FIG. 8A to an expanded state shown in FIG. 8B. The transition may occur, for example, in response to disassembly of the capsule housing 810. Alternatively, in some variations, the collapsed expandable device 854 may be ejected from the capsule housing 810, such as by a spring release triggered by environmental conditions. One or more arrangements of the sealed compartment 820 including at least one tissue penetrating member may be coupled to the expandable device 854 such that expansion of the expandable device 854 actuates the tissue penetrating member (e.g., via one or more drive members within the chamber).

[0055] In some variations, the expansion of the inflatable device 854 may be achieved as a result of the rapid influx of a suitable gas from a chemical reaction. For example, the inflatable device 854 may include multiple compartments that separate reactants that, when mixed, generate a pneumatic output sufficient to inflate the inflatable device 854. The inflatable device 854 may further include a controllable valve or seal that, when opened, allows the reactants to mix and generate a gas to inflate the inflatable device 854. The valve or seal may act as a restraint for an actuator, such that the opening or absence of an element separating the compartments, in turn, activates the inflatable device 854. Alternatively, in some variations, the reactants may be placed in a separate set of compartments that are separate from, but fluidly coupled to, the inflatable device 854, and the resulting output of the reaction may flow into the inflatable device 854.

[0056] Any suitable combination of reactants may be used to generate the expanding gas, for example, one compartment may contain a carbonate (e.g., a metal carbonate) and another compartment may contain an acid, whereby the combination of the two reactants produces carbon dioxide gas.

[0057] 8A and 8B includes one arrangement of tissue-piercing members on one side of the expandable device, it should be understood that in other variations, any suitable number of sealed compartments and / or tissue-piercing members may be arranged in any suitable manner about the expandable device. For example, multiple tissue-piercing members may be arranged circumferentially about the expandable device 854 and / or axially along the expandable device 854. The tissue-piercing members may be evenly (e.g., generally equidistant from one another) and / or unevenly distributed.

[0058] Another example of an expandable device for actuating a tissue-penetrating member is shown in Figures 9A-9C. As shown in Figure 9A, a drug delivery device 900 can include a capsule housing 910 with an expandable device including expandable arms 954. Coupled to each expandable arm 954 is an arrangement of sealed compartments 920 containing one or more tissue-penetrating members (one or more in each expandable arm 954, with three groups of three sealed compartments 920 in each expandable arm 954 shown in Figures 9A-9C as an example). The expandable arms 954 can be biased toward an open or expanded configuration and temporarily restrained by a restraint 960. As above, the restraint 960 can include a biodegradable material.

[0059] Thus, in some variations, after degradation of the capsule housing 910, the restraint 960 may be exposed to conditions (e.g., intestinal conditions) that gradually biodegrade the restraint 960, as shown in FIG 9B. Instead of the capsule housing 910 degrading, in some variations, the restrained expandable device may be expelled from the capsule housing 910, such as by a spring release triggered by environmental conditions. The dissolution of the restraint 960 causes the release of the expandable arms 954, thereby allowing the expandable arms 954 to transition to the expanded configuration.

[0060] The expandable arms 954 may be configured to urge the tissue penetrating member outward (e.g., radially outward) when the expandable arms are in an expanded configuration. For example, as shown in FIG. 9A, the expandable arms 954 may generally pivot radially outward. As another example, the expandable device may include an expandable ring including radially expanding struts or any other suitable structure. The bias to the expanded configuration may be achieved due to inherent shape formations of the expandable arms themselves, biases in any connecting struts between the expandable arms, spring elements coupled to the expandable arms, and the like. In some variations, the expandable arms 954 may be configured to expand outward to similar radial distances when in the expanded configuration, while in some variations, at least some of the expandable arms 954 may be configured to expand outward to different radial distances (e.g., due to at least some of the expandable arms 954 having different lengths, and / or pivot joints of different stiffness, and the like). Further, in some variations, the expandable arms 954 can be configured to expand outward at a similar rate, or some of the expandable arms 954 can be configured to expand outward at different rates.

[0061] While the variations shown in Figures 9A-9C include an expandable device with three expandable arms, it should be understood that in other variations, the expandable device may include any suitable number of expandable arms (e.g., 2, 3, 4, 5, 6 or more) arranged to extend relative to one another. In some variations, the expandable device may include multiple expandable arms that are generally evenly distributed in the circumferential direction (e.g., three expandable arms arranged 120 degrees apart from one another, four expandable arms arranged 90 degrees apart from one another, etc.). Alternatively, the expandable device may include multiple expandable arms that are not evenly distributed in the circumferential direction. Additionally, multiple arrangements of expandable arms may be included in the drug delivery device (e.g., arranged circumferentially and / or axially within the capsule housing volume).

[0062] Additionally, any of the above types of actuators may be combined in any suitable manner to advance the tissue penetrating member into tissue for payload delivery.

[0063] Treatment The methods and devices herein may be used to deliver various types of formulations (e.g., therapeutic drugs). In some variations, drugs that would otherwise be injected (e.g., by chemical degradation in the presence of digestive fluids) may be configured to be released from the tissue-penetrating member for delivery via a drug delivery device as described herein. In some variations, the drug delivery device may be configured to deliver macromolecular peptides and / or proteins. For example, the drug delivery device may be configured to deliver insulin and insulin-related compounds, glucagon-like peptides (e.g., GLP-1, exenatide, etc.), growth hormones (e.g., IGF and / or other growth factors), parathyroid hormone, interferons, chemotherapeutic agents (e.g., interferons), and the like. The therapeutically effective dose contained in the drug delivery device may be determined based on patient characteristics such as age, weight, sex, BMI, etc.

[0064] Furthermore, in some variations, orally administered drugs may be included in the drug delivery device. For example, the drug delivery device may include antibiotics (e.g., penicillin, erythromycin, etc.), antivirals (e.g., protease inhibitors), antiseizure drugs (e.g., furosemide, dilantin, etc.), NSAIDs (e.g., ibuprofen), immunosuppressants, and / or antiparasitics (e.g., antimalarials). Other orally administered drugs, such as painkillers, anti-inflammatory drugs, antihypertensive drugs, etc., may additionally or alternatively be included in the drug delivery device. However, any suitable type of drug, including parenteral drugs that are administered parenterally, may be delivered by the drug delivery device.

[0065] In general, the delivery device may include a capsule housing, at least one tissue penetrating member within a sealed compartment within the capsule housing, and an actuator within the capsule housing and at least partially outside the sealed compartment, such that the actuator is configured to advance the at least one tissue penetrating member from within and out of the sealed compartment. The tissue penetrating member may be configured to release a therapeutic agent. In some variations, the sealed compartment may provide protection for the at least one tissue penetrating member against release of a payload before the tissue penetrating member is advanced into the tissue for release therein.

[0066] One or more components of the delivery device may include a biodegradable material (e.g., a biodegradable polymer). For example, the capsule housing may include a biodegradable polymer. As another example, one or more tissue penetrating members may include a biodegradable polymer. In some variations, for example, the tissue penetrating member may include a biodegradable polymer surrounding a volume of a drug, or a biodegradable polymer having a coating that includes a drug. However, in other variations, the tissue penetrating member may include a drug formed in the penetrating member without a biodegradable material.

[0067] The sealed compartment may be sealed in a variety of ways. For example, in some variations, the sealed compartment may include a first seal, such as a seal disposed at a proximal end of the sealed compartment. Additionally, the sealed compartment may include a second seal, such as a seal disposed at a distal end of the sealed compartment. In some variations, the actuator may be configured to advance at least one tissue penetrating member through the first seal. For example, the actuator may include a drive member configured to steer within the sealed compartment and advance the tissue penetrating member after penetrating the second seal. For example, the first seal and / or the second seal may include a mechanical seal, such as a foil made of aluminum or other suitable material.

[0068] The first seal and / or the second seal may be formed in a variety of suitable ways. For example, one or both seals may be formed by an engineered fit (e.g., a transition fit or an interference fit) between a sealing feature and at least one surface of the sealed compartment. For example, in some variations, the actuator may include a sealing feature such as a drive member having an outer diameter sufficiently oversized relative to an inner wall of the sealed compartment to form a seal.

[0069] In some variations, the delivery device may include multiple tissue penetrating members. For example, each of the multiple tissue penetrating members may be in a respective sealed compartment within the capsule housing. In this example, the delivery device may further include multiple drive members, each configured to advance a respective tissue penetrating member. Alternatively, some or all of the tissue penetrating members may be disposed in a shared sealed compartment and / or advanced by a common drive member or other actuator feature.

[0070] The actuator, in some variations, may include a drive member and an expandable device configured to actuate the drive member. The delivery device may include one or more restraints, the state of which selectively activates the expandable device. For example, the restraint may include a biodegradable material, where degradation of the restraint is configured to activate the expandable device, thereby actuating the drive member (e.g., advancing the tissue penetrating member). The expandable device may include any suitable mechanism, such as a spring, an inflatable device such as a balloon, a lever, an expanding arm, or the like.

[0071] In general, in some variations, a method of delivering a payload to a tissue of a patient includes engulfing a delivery device including a capsule housing, at least one tissue-piercing member configured to release a payload and disposed in a sealed compartment within the capsule housing, and an actuator within the capsule housing and at least partially outside the sealed compartment. The actuator may be configured to advance the at least one tissue-piercing member from within the sealed compartment to release the payload. In some variations, the tissue-piercing member may include a biodegradable polymer surrounding a volume of a drug, or a biodegradable polymer having a coating that includes a drug. However, in other variations, the tissue-piercing member may include a drug formed on the penetrating member. Other suitable variations of delivery devices, such as any of the delivery devices described herein, may also be engulfed and used in the method.

[0072] The sealed compartment of the swallowed device may be sealed in a variety of ways. For example, in some variations, the sealed compartment may include a first seal, such as a seal disposed at a proximal end of the sealed compartment. Additionally, the sealed compartment may include a second seal, such as a seal disposed at a distal end of the sealed compartment. In some variations, the actuator may be configured to advance at least one tissue penetrating member through the first seal. For example, the actuator may include a drive member configured to navigate within the sealed compartment and advance the tissue penetrating member after penetrating the second seal. For example, the first seal and / or the second seal may include a mechanical seal, such as a foil made of aluminum or other suitable material.

[0073] The first seal and / or the second seal may be formed in a variety of suitable ways. For example, one or both seals may be formed by an engineered fit (e.g., a transition fit or an interference fit) between a sealing feature and at least one surface of the sealed compartment. For example, in some variations, the actuator may include a sealing feature such as a drive member having an outer diameter sufficiently oversized relative to an inner wall of the sealed compartment to form a seal.

[0074] In some variations, the swallowed delivery device may include multiple tissue-piercing members, for example, each of the multiple tissue-piercing members may be within a respective sealed compartment within the capsule housing.

[0075] The actuator of the ingested delivery device may, in some variations, include a drive member and an expandable device configured to actuate the drive member. The delivery device may include one or more restraints, the state of which selectively activates the expandable device. For example, the restraint may include a biodegradable material, where degradation of the restraint is configured to activate the expandable device, thereby actuating the drive member (e.g., advancing the tissue penetrating member). The expandable device may include any suitable mechanism, such as a spring, an inflatable device such as a balloon, a lever, an expanding arm, or the like.

[0076] In general, in some variations, a method of delivering a payload to a tissue of a patient includes ingesting a delivery device including a capsule housing, at least one tissue-piercing member configured to release a payload and disposed in a sealed compartment within the capsule housing, and an actuator within the capsule housing. The method further includes disintegrating the capsule housing in the presence of an intestinal environmental condition, and allowing the actuator to advance the at least one tissue-piercing member out of the sealed compartment after the capsule housing disintegrates, thereby releasing the payload. In some variations, the tissue-piercing member may include a biodegradable polymer surrounding a volume of a drug, or a biodegradable polymer having a coating that includes a drug. However, in other variations, the tissue-piercing member may include a drug formed on the penetrating member. Other suitable variations of the delivery device, such as any of the delivery devices described herein, may also be ingested and used in the method.

[0077] In some variations, the actuator may be disposed at least partially outside the sealed compartment. Additionally, in some variations, the actuator may include an expandable device and a restraint, and allowing the actuator to advance the at least one tissue penetrating member may include disassembling the restraint and activating the expandable device. The expandable device may include any suitable mechanism, such as a spring, an inflatable device such as a balloon, a lever, an extension arm, or the like. Also provided is a method of delivering a payload to tissue of a patient, the method comprising engulfing a delivery device comprising a capsule housing, at least one tissue penetrating member configured to release the payload and disposed in a sealed compartment within the capsule housing, and an actuator within the capsule housing and at least partially outside the sealed compartment, the actuator configured to advance the at least one tissue penetrating member out of the sealed compartment to release the payload. The sealed compartment may comprise a first seal, and the actuator may be configured to advance the at least one tissue penetrating member through the first seal. The sealed compartment may comprise a second seal. The delivery device may comprise a plurality of tissue penetrating members. Each of the plurality of tissue penetrating members may be in a respective sealed compartment within the capsule housing. The actuator may comprise a drive member and an expandable device configured to actuate the drive member. The delivery device may further comprise a restraint, and configured to activate the expandable device in the absence of the restraint. The capsule housing may comprise a first biodegradable material and the restraint may comprise a second biodegradable material, and the method may further comprise disintegrating the capsule housing and disintegrating the restraint after disintegrating the capsule housing. The expandable device may comprise at least one of a spring, an inflatable device, and one or more expandable arms. The at least one tissue penetrating member may comprise a biodegradable material surrounding a drug. The at least one tissue penetrating member may comprise a drug formed into a penetrating member shape. The at least one tissue penetrating member may comprise a biodegradable material including a coating including a drug. Further provided is a method of delivering a payload to a patient's tissue, the method comprising: swallowing a delivery device comprising a capsule housing, at least one tissue penetrating member configured to release the payload and disposed in a sealed compartment within the capsule housing, and an actuator within the capsule housing; disintegrating the capsule housing in the presence of intestinal environmental conditions; and after the capsule housing is disintegrated, the actuator advances the at least one tissue penetrating member out of the sealed compartment, thereby releasing the payload. The actuator may be disposed at least partially outside the sealed compartment. The actuator may comprise an expandable device and a restraint, and the actuator advancing the at least one tissue penetrating member may comprise disintegrating the restraint to activate the expandable device. The expandable device may comprise at least one of a spring, an inflatable device, and one or more expandable arms. The at least one tissue penetrating member may comprise a biodegradable material surrounding a drug. The at least one tissue penetrating member may comprise a drug formed into a penetrating member shape. The at least one tissue penetrating member may comprise a biodegradable material including a coating that includes a drug.

[0078] The foregoing description, for purposes of explanation, used specific nomenclature to provide a thorough understanding of the invention. However, it will be apparent to one skilled in the art that specific details are not required to practice the present invention. The foregoing descriptions of specific embodiments of the present invention have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Obviously, many modifications and variations are possible in light of the above disclosure. The embodiments have been selected and described in order to explain the principles of the invention and its practical application, thereby enabling those skilled in the art to utilize the present invention and various embodiments with various modifications as suited to the particular use contemplated. It is intended that the following claims and their equivalents define the scope of the invention.

Claims

1. A delivery device comprising: A capsule housing; at least one tissue penetrating member within a sealed compartment within the capsule housing, the at least one tissue penetrating member configured to release a payload; an actuator within the capsule housing and at least partially outside the sealed compartment, the actuator configured to advance the at least one tissue penetrating member out of the sealed compartment at a distal end; The actuator comprises a drive member and an expandable device configured to actuate the drive member, the expandable device comprising one or more expandable arms, the one or more expandable arms being biased toward an expanded configuration and temporarily restrained by a restraint.

2. The delivery device of claim 1 , wherein the sealed compartment comprises a distal seal at the distal end, and the actuator is configured to advance the at least one tissue penetrating member through the distal seal.

3. The delivery device of claim 2 , wherein the sealed compartment comprises a proximal seal at a proximal end.

4. The delivery device of claim 3 , wherein the actuator comprises a drive member configured to pierce the proximal seal.

5. The delivery device of claim 3 , wherein the proximal seal is formed by an engineered fit between a sealing feature and at least one surface of the sealed compartment.

6. The delivery device of claim 5 , wherein the actuator comprises the sealing feature.

7. The delivery device of claim 3 , wherein at least one of the distal seal and the proximal seal comprises a foil.

8. The delivery device of claim 3 , wherein at least one of the distal seal and the proximal seal comprises a biodegradable material.

9. The delivery device of claim 1 , comprising a plurality of tissue penetrating members.

10. The delivery device of claim 9 , wherein each of the plurality of tissue penetrating members is within a respective sealed compartment within the capsule housing.

11. The delivery device of claim 9 , comprising a plurality of drive members, each drive member configured to advance a respective tissue penetrating member.

12. The delivery device of claim 1 , wherein the restraint comprises a biodegradable material and is configured to activate the expandable device upon degradation of the restraint.

13. The delivery device of claim 1 , wherein the one or more expandable arms are configured to urge the at least one tissue penetrating member radially outward when expanded.

14. The delivery device of claim 1 , wherein the capsule housing comprises a biodegradable polymer.

15. The delivery device of claim 1 , wherein the at least one tissue-penetrating member comprises a biodegradable material that surrounds a drug.

16. The delivery device of claim 1 , wherein the at least one tissue penetrating member comprises a drug formed into a penetrating member shape.

17. The delivery device of claim 1 , wherein the at least one tissue-penetrating member comprises a biodegradable material including a coating comprising a drug.

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