WO2008073806A1

WO2008073806A1 - Active transdermal drug delivery system

Info

Publication number: WO2008073806A1
Application number: PCT/US2007/086636
Authority: WO
Inventors: Robert Gordon Butterfield; Michael Charles
Original assignee: Sabic Innovative Plastics Ip B.V.
Priority date: 2006-12-08
Filing date: 2007-12-06
Publication date: 2008-06-19

Abstract

A transdermal drug delivery system (100) that provides a self-regulatmg closed loop system for the delivery of drugs or other therapeutic agents through a user's skin. The transdermal system includes a substrate (105), a sensing system (115) for detecting the saturation level of the therapeutic agent in an individual's blood stream, and a drug delivery system for increasing the amount of therapeutic agent delivered to the individual using the transdermal system. Using a transdermal system that has a self-contained sensing system and drug delivery system, the transdermal systems of the present invention do not require external monitors and/or power supplies, such that the resulting transdermal systems are closed-loop and self -regulating.

Description

ACTIVE TRANSDERMAL DRUG DELIVERY SYSTEM

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 60/869,159 filed December 8, 2006, which is hereby incorporated by reference in its entirety.

FIELD OF INVENTION

[0002] The present invention relates to drug delivery systems and, in particular, to self-regulating drug delivery systems.

BACKGROUND OF INVENTION

[0003] The use of drug delivery systems for delivering therapeutic agents through the skin of an individual is well known. These drug delivery systems can be classified into two groups - passive and active.

[0004] One approach to the delivery of a therapeutic agent through the sldn is the use of a passive transdermal delivery system such as transdermal patches. Generally, transdermal patches contain a therapeutic agent and an adhesive that allows the transdermal device to adhere to the skin of a patient, allowing for the passage of the therapeutic agent from the device through the skin of the patient. Various advantages of using transdermal patches include constant rate of delivery of the therapeutic agent, longer duration of action, non-invasive application, improved patient compliance, and the supply of therapeutic agent may be interrupted at any time by tearing off the system. One advantage of transdermal patches is the fact that the therapeutic agent can be delivered to the bloodstream without traversing the gastrointestinal tract and avoiding a "first pass" through the hepatic system prior to reaching the target site. This helps avoid any gastrointestinal incompatibility with the therapeutic agents and unwanted destruction of the therapeutic agents by metabolism in the gastrointestinal tract. [0005] Once the therapeutic agent has penetrated the sldn layer, it is absorbed into the blood stream. In addition, transdermal absorption minimizes inter- and intra- patient variations regarding such incompatibilities and metabolisms. By using transdermal absorption, it is possible to provide more consistent therapeutic agent delivery to the individual and to realize a greater pharmaceutical efficiency. In addition, it is possible to provide effective dosing of therapeutic agent. However, with passive systems, it is not possible to regulate the delivery of the therapeutic agent itself as compared to a desired therapeutic agent concentration level in the patient. The patch is designed to deliver a relatively consistent rate of the therapeutic agent as the patch is worn, regardless of the level of the therapeutic agent in the patient's blood stream. As such, if the level becomes excessive, the only way to stop delivery of the therapeutic agent is to remove the patch. And if the level becomes too low, there are no mechanisms provided to alert the patient or treatment professional of this condition.

[0006] One alternative, at least in regards to the delivery of the therapeutic agent, is to provide a more active system to control the delivery of the therapeutic agent at selected intervals. In this embodiment, a control system may be provided to alert the wearer of the patch or a treatment professional that the therapeutic agent is no longer present in the blood stream. At that point, a new patch may be applied or, in the alternative, a mechanism may be activated to increase the transfer of the therapeutic agent into the blood stream. One such mechanism is iontophoresis. Iontophoresis is a technique employed for enhancing the flux of ionized substances through membranes by application of electric current. The principal mechanisms by which iontophoresis enhances molecular transport across the skin are (a) repelling a charged ion from an electrode of the same charge, (b) electroosmosis - the convective movement of solvent that occurs through a charged pore in response the preferential passage of counter-ions when an electric field is applied, or (c) increase skin permeability due to application of electrical current or heat. Iontophoresis is used to open pores and increase the rate of therapeutic agent delivery. However, many of these systems require an active step on behalf of the patient and can result in levels of the therapeutic agent dropping too low if there is a significant delay between detection of a low level of therapeutic agent and activation of the device.

[0007] Another problem with passive transdermal patches is the fact that these systems can only effectively deliver small molecule therapeutic agents. Larger molecule therapeutic agents are not easily passed into the blood stream through the pores of the skin. As discussed, iontophoresis may be used to enhance the molecular transport across the skin of larger molecules by opening the pores to permit larger molecules to pass through. However, as previously discussed, many prior art iontophoresis systems require an active step on behalf of the patient and can result in levels of the therapeutic agent dropping too low if there is a significant delay between detection of a low level of therapeutic agent and activation of the device.

[0008] However, as with the prior art systems, these mechanisms are not self-regulating. While larger molecule therapeutic agents can be delivered, their delivery often requires an active step by the patient or the treatment professional to activate the device to cause the pores to be forced open to drive the larger molecule therapeutic agent into the blood stream.

[0009] Accordingly, it would be beneficial to provide a drug delivery system that is self-regulating. It would also be beneficial to provide a drug delivery system that was capable of delivering large molecule therapeutic agents. It would also be beneficial to provide a drug delivery system that did not require an active step by the patient or the treatment professional to activate the device. It would also be beneficial to provide a drug delivery system that was better able to maintain a relatively constant level of treatment agent in the patient.

SUMMARY OF THE INVENTION

[0010] The present invention addresses the issues associated with the prior art by providing a transdermal drug delivery system that provides a self-regulating closed-loop system for the delivery of drugs or other therapeutic agents through a user's skin. The drug delivery system includes a sensing system and a drug delivery system within the transdermal system such that the transdermal systems do not require external monitors/sensors and/or power supplies. As such, the transdermal systems are more active than passive systems by being able to increase the rate of therapeutic agent transferred to the individual when the system detects that the level of therapeutic agent has dropped outside a preset threshold level, thereby enabling a more consistent dosing of the therapeutic agent to occur. In addition, since the transdermal system is self-regulating, additional therapeutic agent can be delivered without the requirement of an active step by the patient or the treatment professional, again enabling a more consistent dosing of the therapeutic agent to occur.

[0011] Accordingly, in one aspect, the present invention provides a drug delivery system that includes a substrate for contacting an individual's skin, a sensing system for detecting a level for a selected therapeutic agent in the individual's blood stream, and a therapeutic agent delivery system that is activated by input from the sensing system, wherein the therapeutic agent delivery system is capable of delivering an additional amount of the therapeutic agent to the individual's blood stream if the detected level for the selected therapeutic agent is below a selected threshold.

BRIEF DECRIPTION OF THE DRAWINGS

[0012] Figure 1 is a perspective view of a drug delivery system according to one embodiment of the present invention.

[0013] Figure 2 is a top view of a drug delivery system according to another embodiment of the present invention.

[0014] Figure 3 is a close-up view of an electrode system used in the drug delivery system embodiment shown in Figure 2.

DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention is more particularly described in the following description and examples that are intended to be illustrative only since numerous modifications and variations therein will be apparent to those skilled in the art. As used in the specification and in the claims, the singular form "a," "an," and "the" may include plural referents unless the context clearly dictates otherwise. Also, as used in the specification and in the claims, the term "comprising" may include the embodiments "consisting of and "consisting essentially of." Furthermore, all ranges disclosed herein are inclusive of the endpoints and are independently combinable.

[0016] As used herein, approximating language may be applied to modify any quantitative representation that may vary without resulting in a change in the basic function to which it is related. Accordingly, a value modified by a term or terms, such as "about" and "substantially," may not to be limited to the precise value specified, in some cases. In at least some instances, the approximating language may correspond to the precision of an instrument for measuring the value.

[0017] The present invention provides a transdermal system that includes a drug delivery system that uses a self-regulating closed loop system for the delivery of drugs or other therapeutic agents through a user's skin. The transdermal system includes a substrate, a sensing system for detecting the saturation level of the therapeutic agent in an individual's blood stream, and a drug delivery system for increasing the amount of therapeutic agent delivered to the individual using the transdermal system. Using a transdermal system that has a self-contained sensing system and drug delivery system, the transdermal systems of the present invention do not require external monitors and/or power supplies, such that the resulting transdermal systems are closed-loop and self-regulating, unlike prior art transdermal patches.

[0018] In one aspect of the present invention, the transdermal systems include a drug delivery system. The "drug delivery system" may be any system capable of causing a therapeutic agent to be transferred through the sldn into the blood stream of an individual at a rate faster than the transfer of the therapeutic agent through the skin using a passive transdermal patch having no drug delivery system. In one embodiment, the drug delivery system includes a heat-generating mechanism that applies heat to the individual's skin to open pores in the skin. In another embodiment, the drug delivery system includes an electric current-generating mechanism that applies electric current to the individual's skin to open pores in the skin. In yet another exemplary embodiment, the drug delivery system includes an artificial muscle system that is designed to force the therapeutic agent through the pores using force generated by the artificial muscle.

[0019] Accordingly, in one embodiment, the drug delivery system includes a heat-generating or an electric current-generating mechanism for opening the pores of an individual's skin. In one embodiment, the electric current-generating mechanism includes an electrode or electric wire to which an electric charge is supplied, such as using a power source. The electric charge stimulates the pores of the individual causing them to open. In another embodiment, the heat-generating mechanism also includes an electrode or electric wire to which an electric charge is supplied. Li this embodiment, the electric charge causes the electrode or electric wire to heat, or causes the material surrounding the electrode or electric wire to heat, and wherein the heat opens the pores of the individual thereby enabling the faster transfer of the therapeutic agent there through.

[0020] Nevertheless, in an exemplary embodiment, the drug delivery system includes an artificial muscle. An "artificial muscle" is a device that, upon application of an electric current, can be caused to contract and release, thereby enabling a therapeutic agent to be forced through the pores of an individual. In one embodiment, the artificial muscle includes films of electroactive silicone or acrylic polymers that flatten and stretch up to three times their original size in the presence of an electric current. In alternative embodiments, the elctroactive polymers include, but are not limited to, ionic polymeric membrane composites, polypyrrole, piezoelectric actuators, or a combination including at least one of the foregoing polymers. In yet other alternative embodiments, the elctroactive polymers may include one or more fillers, such as carbon fibers or aramid fibers.

[0021] hi use, the power supply of the transdermal system is used to provide the electric current to activate the artificial muscle, causing it to expand and contract as needed to drive the therapeutic agent into and through the pores of an individual. Depending on the type of artificial muscle used and the size of the molecules of the therapeutic agent, the articifical muscle may, in select embodiments, be sufficiently powerful to force larger molecule therapeutic agents through the pores of the skin that would otherwise not normally pass through these pores through natural transmission.

[0022] Accordingly, in another aspect, the drug delivery system of the present invention includes a power source for powering the drug delivery system. In one embodiment, the power source is a battery, such as an alkaline or lithium battery. In another embodiment, the power source is a solar cell that stores energy from solar light that may then be used to power the drug delivery system when activated. In still another embodiment, the power source is an autobiofuel cell. The autobiofuel cell includes a biochemical fuel cell substance creating a battery power source, which may then be used to power the drug delivery system when activated, hi general, any portable power source that is capable of providing power to a drug delivery system, such as an electrode or an artificial muscle, may be used in the present invention.

[0023] The drug delivery system used in the present invention may be used to deliver small molecule therapeutic agents, large molecule therapeutic agents, or both. As used herein, a "therapeutic agent" is any constituent that may provide therapeutic effects to an individual, depending on the benefits desired. In one embodiment, the therapeutic agent is a drug, such as a treatment drug or a pain relief agent, hi another embodiment, the therapeutic agent is a hormone, hi still another embodiment, the therapeutic agent is a vitamin. Other alternative embodiments of the therapeutic agent include, but are not limited to, a RNA string, a DNA string, a protein-based molecule, fungicides, bactericides, bacteriostatics, antibiotics, antipyretics, antidiabetic agents, coronary vasodilators, cardio-active glycosides, spasmolytics, hypotensives, psychotropics, migraine analgesics, corticoids, analgesics, contraceptives, antirheumatics, cholinergics or anticholinergics, symphaticomimetics or symphaticolytics, vasodilators, anticoagulants, or antiarrythmics. In general, a therapeutic agent includes any constituent capable of being delivered using a transdermal drug delivery system.

[0024] Accordingly, in another aspect, the drug delivery system may, in some embodiments, provide a storage device for storing the therapeutic agent to be delivered. While it is contemplated that the therapeutic agent may be located on a surface of the transdermal system in thin layer, depending on the type of therapeutic agent to be delivered and/or the amount of therapeutic agent to be delivered, the drug delivery system may also include, in alternative embodiments, a storage device for storing excess therapeutic agent to be delivered. In one embodiment, the storage device includes a reservoir that contains the therapeutic agent to be delivered. In an alternative device, the storage area includes a foam material in which the therapeutic agent to be delivered is located. Other embodiments may include other storage devices known for storing a therapeutic agent to be delivered.

[0025] In addition to the drug delivery system, the transdermal systems of the present invention also include a sensing system for detecting the level of a therapeutic agent in an individual's blood stream to then determine whether the drag delivery system should be activated to increase the amount of therapeutic agent delivered to the individual. The sensing system includes at least one sensor capable of detecting the level of a therapeutic agent in an individual's blood and a controller for comparing the actual level of the therapeutic agent in the individual's blood with a selected level of the therapeutic agent in the individual's blood. If the sensed level falls within the selected level, nothing is done. Conversely, if the sensed level of the therapeutic agent in the individual's blood is outside the selected level of the therapeutic agent in the individual's blood, then the control system activates the drug delivery system to increase the rate at which the therapeutic agent is transferred into the individual's blood stream.

[0026] Accordingly, in one aspect, the sensing system includes a sensor capable of detecting the level of a therapeutic agent in an individual's blood stream, hi one embodiment, the sensing system includes one or more microneedles that are capable of piercing the skin or otherwise contacting an individual's blood. The blood to be tested may then, in one embodiment, be passed through tiny holes in the microneedles to travel to the sensor or may, in another embodiment, flow around the microneedles to travel to the sensor. The sensor then analyzes the blood, such as through the use of a biosensor capable of determining the presence and amount of a selected therapeutic agent in the individual's blood stream, which then sends this detected level to a control system. [0027] In another embodiment, the sensing system includes an electromagnetic sensor capable of detecting the level of a selected therapeutic agent in an individual's bloodstream. This detected level would, again, be sent to a control system.

[0028] The control system includes, in one embodiment, a microcontroller capable of comparing the detected level of the therapeutic agent in the individual's blood stream with a preset threshold level. The microcontroller is also capable of activating the power supply that operates the drug delivery system if the detected level of the therapeutic agent in the individual's blood stream is outside the preset threshold level.

[0029] The transdermal system also includes a substrate that is designed to contact the skin. The substrate is, in one embodiment, simply selected to provide a carrier for the drug delivery system and the sensing system. In an alternative embodiment, the substrate is selected such that the therapeutic agent is capable of being transmitted there through and into the pores of an individual for delivering the therapeutic agent.

[0030] Accordingly, in one embodiment, the substrate is a material, such as an organic polymer, that provides sufficient flexibility for the transdermal patch to be attached to an individual's skin while also providing sufficient protection for the drug delivery system and the sensing system. Examples of organic polymers that can be used include, but are not limited to, polyolefins such as polyethylene, polypropylene; polyamides such as Nylon 4,6, Nylon 6, Nylon 6,6, Nylon 6, 10, Nylon 6, 12; polyesters such as polyethelene terephthalate (PET), polybutylene terephthalate (PBT), poly( 1 ^-cyclohexane-dimethanol- 1 ,4-cyclohexanedicarboxylate) (PCCD), poly(trimethylene terephthalate) (PTT), poly(cyclohexanedimethanol-co-ethylene terephthalate) (PETG), polyethylene naphthalate) (PEN), poly(butylene naphthalate) (PBN); polyarylates, polyimides, polyacetals, polyacrylics, polycarbonates (PC), polystyrenes, polyamideimides, polyacrylates, polymethacrylates such as polymethylacrylate, or polymethylmethacrylate (PMMA); polyarylsulfones, polyethersulfones, polyphenylene sulfides, polyvinyl chlorides, polysulfones, polyimides, polyetherimides, polytetrafluoroethylenes, polyetherketones, polyether etherketones, polyether ketone ketones, polybenzoxazoles, polyoxadiazoles, polybenzothiazinophenothiazines, polybenzothiazoles, polypyrazinoquinoxalines, polypyromellitimides, polyquinoxalines, polybenzimidazoles, polyoxindoles, polyoxoisoindolines, polydioxoisoindolines, polytriazines, polypyridazines, polypiperazines, polypyridines, polypiperidines, polytriazoles, polypyrazoles, polypyrrolidines, polycarboranes, polyoxabicyclononanes, polydibenzofurans, polyphthalides, polyacetals, polyanhydrides, polyvinyl ethers, polyvinyl thioethers, polyvinyl alcohols, polyvinyl ketones, polyvinyl halides, polyvinyl nitriles, polyvinyl esters, polysulfonates, polysulfides, polythioesters, polysulfones, polysulfonarnides, polyureas, polyphosphazenes, polysilazanes, polysiloxanes, polyolefins, or the like, or a combination including at least one of the foregoing organic polymers.

[0031] The substrates may, in alternative embodiments, include one or more fillers to provide additional characteristics to the substrate. For example, in those embodiments wherein the drug delivery system include heat or electric current- generating mechanisms, a conductive filler may be included to enhance the transfer of the electric current, thereby enabling a more uniform heating of the individual's skin. Examples of conductive fillers include ceramic fillers, metal fillers, carbonaceous fillers, or a combination including at least one of the foregoing fillers. Examples of ceramic fillers include, but are not limited to, titanium diborides (TiB₂) tungsten carbide (WC), tin oxide, indium tin oxide (ITO), antimony tin oxide, titanium nitride (TiN), zirconium nitride (ZrN), titanium carbide (TiC), molybdenum suicide (MoSi₂), potassium titanate whiskers, vanadium oxides (V₂O₃), or a combination including at least one of the foregoing ceramic fillers. Examples of metal fillers include, but are not limited to, silver, vanadium, tungsten, nickel, or the like, or a combination including at least one of the foregoing metals. Metal alloys can also be added to the polymeric PTC composition. Examples of metal alloys include stainless steel, neodymium iron boron (NdFeB), samarium cobalt (SmCo), aluminum nickel cobalt (AlNiCo), or the like, or a combination including at least one of the foregoing. Examples of carbonaceous fillers include, but are not limited to, carbonaceous fillers such as for example carbon black, metal coated fillers, carbon nanotubes, graphite, or the like, or a combination including at least one of the foregoing carbonaceous fillers.

[0032] In an alternative embodiment, the fillers include fillers designed to provide alternative characteristics, such as silver-containing fillers to provide antimicrobial characteristics. Examples of silver-containing fillers include, but are not limited to, silver particles, silver fibers, silver-coated fibers, or a combination including at least one of the foregoing silver-containing fillers.

[0033] The substrate may also include an adhesive material for better attachment of the transdermal system to the individual's skin. Examples of adhesive materials that may be used include pressure-sensitive adhesive materials. The pressure-sensitive adhesive materials include, in one embodiment, a polymer matrix having a base polymer and optional conventional additives. Suitable materials include, for example, silicones, rubber, rubber-like synthetic homo-, co-, or block polymers, polyacrylates and their copolymers, and also esters of hydrogenated colophony. Basically, any polymer is suitable that is used in the production of pressure-sensitive adhesives and that is physiologically acceptable. Examples of adhesives that may be used in the present invention include, but are not limited to, acrylic adhesives, vinyl acetate adhesives, silicone or synthetic adhesives, natural rubber adhesives, or a combination including at least one of the foregoing adhesives.

[0034] hi some embodiments, the adhesive is selected to enhance the transfer of the therapeutic agent through the wearer's skin. As such, the adhesive may be located on all or substantially all of the surface of the substrate closest to the individual, hi an alternative embodiment, the adhesive is located on only a portion of the substrate, such as around the periphery of the substrate.

[0035] hi an alternative embodiment, the adhesive layer includes a mechanism for indicating the length of time that the transdermal patch has been in use. As such, the transdermal system can provide a visual indicator, such as a color change, that may be used to help regulate the frequency with which the transdermal system is replaced. In one embodiment, the visual indicator includes one or more components in the adhesive layer and wherein these components react with oxygen or another gas in the air. The reaction of the oxygen with the added components creates a color shift and/or an opacity shift of the substrate. The duration and/or rate of the oxidation can be modified such that it is based on the average absorption rate of the drug. The color and/or opacity shift can be used as a visual indicator to indicate when it is time to replace the patch. In one embodiment, the added component includes a leuco dye such as methylene blue, Brilliant Cresyl Blue, Toluidine Blue O, Basic Blue 3, Methylene Green, Taylor's Blue, Janus Green B, Meldola's Blue, Thionin, Nile Blue, and Celestine Blue. In an alternative embodiment, the added component includes a blocked leuco dye. Additional components include, but are not limited to, oxygen scavengers, antioxidents, pH modifiers, or a combination thereof.

[0036] In addition, the adhesive layer may include a skin penetration enhancer designed to facilitate transfer of the therapeutic agent into the blood stream of the individual. Examples of skin penetration enhancers include, but are not limited to, N- methyl-2-pyrrolidone, oleic acid and l-dodecyl-azacycloheptan-2-one, oleyl alcohol, or a combination including at least one of the foregoing skin penetration enhancers.

[0037] The foregoing and other features of the present invention will be more readily apparent from the following detailed description and drawings of the illustrative embodiments of the invention wherein like reference numbers refer to similar elements.

[0038] Figure 1 provides one embodiment of a transdermal system. In this embodiment, the transdermal system 100 includes a substrate 105 optionally made from an organic polymer. The transdermal system 100 includes a sensing system that includes a plurality of microneedles 110 on the substrate 105 that are designed to be capable of piercing the skin of an individual to enable contact with the individual's blood stream to occur. At least some of the microneedles 110 are in contact with a sensor 115, such as a biosensor, capable of detecting a level of therapeutic agent in the individual's blood stream. The data from the sensor 115 is sent to a microcontroller 120 that is capable of comparing the detected level of therapeutic agent in the individual's blood stream to a preset threshold level of therapeutic agent in the individual's blood stream. If the detected level is within the threshold level, the microcontroller 120 does nothing. However, if the detected level is outside the threshold level, the microcontroller 120 is capable of activating a power supply 125, in this embodiment shown as a battery, that then supplies power to a drug delivery system. In this embodiment, the drug delivery system includes an artificial muscle 130 that is capable of delivering therapeutic agent to the substrate.105 to be delivered to the individual's blood streams through direct contact of the therapeutic agent with the skin, or through one or more holes in the microneedles 110. This embodiment may continue to be used to deliver therapeutic agent to the individual's blood stream until the therapeutic agent is completely delivered or until the power supply is exhausted, all without the need for external sensing devices and/or power devices.

[0039] In an alternative embodiment, which is shown in Figures 2 and 3, the transdermal system 200 also includes a substrate 205 on which the sensing system and the drug delivery system are located. In this embodiment, the transdermal system includes a reservoir 235 for containing the therapeutic agent to be delivered and uses an electrode 240 as part of the drug delivery system. As with the embodiment in Figure 1, the transdermal system includes a sensing system 215. In this embodiment, the sensing system 215 includes an electro-magnetic sensor (not shown) for detecting the level of the therapeutic agent in the individual's blood stream. Data from the electro-magnetic sensor is sent to a microcontroller 220 that is capable of comparing the detected level of therapeutic agent in the individual's blood stream to a preset threshold level of therapeutic agent in the individual's blood stream. If the detected level is within the threshold level, the microcontroller 220 does nothing. However, if the detected level is outside the threshold level, the microcontroller 220 is capable of activating a power supply 225 that then supplies power to the electrode 240 that provide heat and/or electric current to the individual's sldn to open pores and promote an increase in the rate at which the therapeutic agent is delivered to the individual's blood stream. As with the embodiment in Figure 1, the transdermal system 200 continues to operate until the therapeutic agent is completely delivered or until the power supply is exhausted, all without the need for external sensing devices and/or power devices. [0040] This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to make and use the invention. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims. All citations referred herein are expressly incorporated herein by reference.

Claims

1. A transdermal drug delivery system comprising:

a substrate for contacting an individual's skin;

a sensing system for detecting a level for a selected therapeutic agent in the individual's blood stream; and

a therapeutic agent delivery system that is activated by input from the sensing system, wherein the therapeutic agent delivery system is capable of delivering an additional amount of the therapeutic agent to the individual's blood stream if the detected level for the selected therapeutic agent is below a selected threshold.

2. The transdermal drug delivery system of claim 1, wherein the therapeutic agent is selected from a drug, a vitamin, a hormone, a RNA string, a DNA string, a protein-based molecule or a combination comprising at least one of the foregoing therapeutic agents.

3. The transdermal drug delivery system of any of claims 1 — 2, wherein the sensing system includes one or more microneedles for contacting an individual's blood to help detect the level for the selected therapeutic agent in the individual's blood stream.

4. The transdermal drag delivery system of any of claims 1 - 3, wherein the sensing system includes an electro-magnetic sensor for detecting the level for the selected therapeutic agent in the individual's blood stream.

5. The transdermal drag delivery system of any of claims 1 — 4, wherein the sensing system includes a microcontroller for comparing a detected level of the therapeutic agent in the individual's blood stream with the selected threshold level of the therapeutic agent in the individual's blood stream and wherein the microcontroller is capable of activating the drug delivery system if the detected level for the selected therapeutic agent is below the selected threshold level.

6. The transdermal drug delivery system of any of claims 1 - 5, wherein the therapeutic agent delivery system includes a power supply for assisting in the delivering of additional therapeutic agent to the individual's blood stream.

7. The transdermal drug delivery system of claim 6, wherein the power supply comprises a battery.

8. The transdermal drug delivery system of any of claims 6 - 7, wherein the power supply comprises a solar panel.

9. The transdermal drug delivery system of any of claims 1 - 8, wherein the sensing system comprises a biosensor.

10. The transdermal drug delivery system of any of claims 1 - 9, wherein the substrate includes a pressure-sensitive adhesive.

11. The transdermal drug delivery system of any of claims 1 - 10, wherein the therapeutic agent delivery system includes an artificial muscle that contracts when a current is applied to it.