Functionalized microneedles transdermal drug delivery systems, devices, and methods

• US 20070078376A1
• Filed: 09/12/2006
• Published: 04/05/2007
• Est. Priority Date: 09/30/2005
• Status: Abandoned Application

• Current Assignee: TTI Ellebeau, Inc. (Ease Asset Management Ltd.)
• Original Assignee: TTI Ellebeau, Inc. (Ease Asset Management Ltd.)
• Inventors: Smith, Gregory
• Application Number:
  US11/520,855
• Publication Number:
  US 20070078376A1
• Time in Patent Office: Days
• US Class Current: 604/21
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body

Abstract

Systems, devices, and methods for transdermal delivery of one or more therapeutic active agents to a biological interface. A transdermal drug delivery system is operable for delivering of one or more therapeutic active agents to a biological interface. The system includes an active electrode assembly, a counter electrode assembly, and a plurality of functionalized microneedles.

Claims

1. A transdermal drug delivery system for delivering of one or more therapeutic active agents to a biological interface, comprising:

a surface functionalized substrate having a first side and a second side opposing the first side, the surface functionalized substrate comprising a plurality of microneedles projecting outwardly from the first side, each microneedle having an outer surface and an inner surface that forms a channel, the channel operable for providing fluidic communication between the first and the second sides of the surface functionalized substrate, at least one of the inner surface or the outer surface comprising one or more functional groups.

2. The transdermal drug delivery system of claim 1, wherein the one or more functional groups are selected from charge functional groups, hydrophobic functional groups, hydrophilic functional groups, chemically reactive functional groups, organofunctional group, and bio-compatible groups.

3. The transdermal drug delivery system of claim 1, wherein the one or more functional groups are selected from the following Formula I alkoxysilanes:

(R²)Si(R¹)₃  

 

(Formula I)

wherein,

R¹ is selected from a chlorine, an acetoxy and alkoxy; and

R² is selected from an organofunctional group, an alkyl, an aryl, an amino, a methacryloxy, and an epoxy.

4. The transdermal drug delivery system of claim 1, wherein the surface functionalized substrate comprises at least one material selected from ceramics, metals, polymers, molded plastics, and superconductor wafers.

5. The transdermal drug delivery system of claim 1, wherein the surface functionalized substrate comprises at least one material selected from elastomers, epoxy photoresist, glass, glass polymers, glass/polymer materials, chromium, cobalt, gold, molybdenum, nickel, stainless steel, titanium, tungsten steel, biodegradable polymers, non-biodegradable polymers, organic polymers, inorganic polymers, silicon, silicon dioxide, polysilicon, silicon-based organic polymers, silicon rubbers, superconducting materials, or combinations, composites, and alloys thereof.

6. The transdermal drug delivery system of claim 1, further comprising:

an active electrode assembly including at least one active electrode element; and

a counter electrode assembly including at least one counter electrode element.

7. The transdermal drug delivery system of claim 6, wherein the active electrode assembly further comprises:

at least one active agent reservoir; and

wherein the surface functionalized substrate is positioned between the active electrode assembly and the biological interface, and the at least one active electrode element is operable to provide an electromotive force to drive an active agent from the at least one active agent reservoir, through the plurality of microneedles, and to the biological interface.

8. The transdermal drug delivery system of claim 7, further comprising:

one or more active agents loaded in the at least one active agent reservoir.

9. The transdermal drug delivery system of claim 7, wherein the one or more therapeutic active agents are selected from cationic, anionic, ionizable, or neutral active agents.

10. The transdermal drug delivery device of claim 7, wherein the one or more active agents are selected from analgesics, anesthetics, anesthetics vaccines, antibiotics, adjuvants, immunological adjuvants, immunogens, tolerogens, allergens, toll-like receptor agonists, toll-like receptor antagonists, immuno-modulators, immuno-response agents, immuno-stimulators, specific immuno-stimulators, non-specific immuno-stimulators, and immuno-suppressants, or combinations thereof.

11. The transdermal drug delivery system of claim 7, wherein the one or more therapeutic active agents are cationic, and the one or more functional groups take the form of negatively charged functional groups.

12. The transdermal drug delivery system of claim 6, further comprising:

a power source electrically coupled to the at least one active and the at least one counter electrode elements.

13. The transdermal drug delivery system 12 wherein the power source comprises at least one of a chemical battery cell, super- or ultra-capacitor, a fuel cell, a secondary cell, a thin film secondary cell, a button cell, a lithium ion cell, zinc air cell, and a nickel metal hydride cell.

14. A microneedle structure, comprising:

a substrate having an exterior and an interior surface, a first side, and a second side opposing the first side; and

a plurality of microneedles projecting outwardly from the first side of the substrate, each microneedle having a proximate and a distal end, an outer surface and an inner surface forming a channel exiting between the proximate and the distal ends to provided fluid communication there between;

wherein at least the inner surface of the microneedles is modified with one or more functional groups.

15. The microneedle structure of claim 14 wherein each microneedle is substantially hollow, and each microneedle is substantially in the form of a frusto-conical annulus.

16. The microneedle structure of claim 14 wherein the plurality of microneedles is integrally formed from the substrate.

17. The microneedle structure of claim 14 wherein the plurality of microneedles are arranged in the form of an array.

18. The microneedle structure of claim 14 wherein at least the interior surface of the substrate is modified with a sufficient amount of one or more functional groups.

19. The microneedle structure of claim 14, wherein the substrate comprises at least one material selected from ceramics, elastomers, epoxy photoresist, glass, glass polymers, glass/polymer materials, metals, chromium, cobalt, gold, molybdenum, nickel, stainless steel, titanium, tungsten steel, molded plastics, polymers, biodegradable polymers, non-biodegradable polymers, organic polymers, inorganic polymers, silicon, silicon dioxide, polysilicon, silicon-based organic polymers, silicon rubbers, superconducting materials, superconducting wafers, or combinations, composites, and alloys thereof.

20. The microneedle structure of claim 14 wherein the one or more functional groups are selected from charge functional groups, hydrophobic functional groups, hydrophilic functional groups, chemically reactive functional groups, organofunctional group, and bio-compatible groups.

21. A method of forming an iontophoretic drug delivery device for providing transdermal delivery of one or more therapeutic active agents to a biological interface, comprising:

forming a plurality of hollow microneedles, having an interior and an exterior surface on a substrate having a first side and a second side opposing the first side, the plurality of hollow microneedles substantially formed on the first side of the substrate;

functionalizing at least the interior surface of the plurality of hollow microneedles to include one or more functional groups; and

physically coupling the substrate to an active electrode assembly, the active electrode assembly including at least one active agent reservoir and at least one active electrode element, the at least one active agent reservoir in fluidic communication with the plurality of hollow microneedles, the at least one active electrode element operable to provide an electromotive force to drive an active agent from the at least one active agent reservoir, through the plurality of hollow microneedles, and to the biological interface.

22. The method of claim 21 wherein forming a plurality of hollow microneedles comprises:

forming a photoresist mask for patterning the exterior surface of the plurality of hollow microneedles on the first side of the substrate;

forming a photoresist mask for patterning the interior surface of the plurality of hollow microneedles on the second side of the substrate;

etching the interior surface of the plurality of the hollow microneedles on the second side of the substrate; and

etching the exterior surface of the plurality of the hollow microneedles on the first side of the substrate.

23. The method of claim 21, wherein functionalizing at least the interior surface of the plurality of hollow microneedles comprises:

modifying at least the interior surface of the plurality of hollow microneedles to comprise one or more functional groups selected from charge functional groups, hydrophobic functional groups, hydrophilic functional groups, chemically reactive functional groups, organofunctional groups, and water-wettable groups.

24. The method of claim 21 wherein functionalizing at least the interior surface of the plurality of hollow microneedles comprises:

hydrolyzing one or more silane coupling agents comprising at least one functional group to form silanols; and

coupling the silanols to at least the interior surface of the plurality of hollow microneedles.

25. The method of claim 24 wherein the silane coupling agents are selected from Formula I alkoxysilanes:

(R²)Si(R¹)₃  

 

(Formula I)

wherein,

R¹ is selected from a chlorine, an acetoxy, and an alkoxy; and

R² is selected from an organofunctional group, an alkyl, an aryl, an amino, a methacryloxy, and an epoxy.

26. The method of claim 21 wherein functionalizing at least the interior surface of the plurality of hollow microneedles comprises:

providing an effective amount of a functionalizing agent comprising a functional group, and a binding group; and

coupling the functionalizing agent to at least the interior surface of the plurality of hollow microneedles.