High-Aspect-Ratio Microdevices and Methods for Transdermal Delivery and Sampling of Active Substances

• US 20050261632A1
• Filed: 05/18/2005
• Published: 11/24/2005
• Est. Priority Date: 05/18/2004
• Status: Active Grant

• Current Assignee: Bai Xu
• Original Assignee: Bai Xu
• Inventors: Xu, Bai
• Granted Patent: US 7,591,806 B2
• Time in Patent Office: Days
• US Class Current: 604/173
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

High-aspect-ratio microdevices comprising microneedles, microknives and microblades and their manufacturing methods are disclosed. These devices can be used for the delivery of therapeutic agents across the skin or other tissue barriers to allow chemical and biological molecules getting into the circulation systems. The microneedles can also be used to withdraw body fluids for analysis of clinically relevant species when the device has an integrated body fluid sensor or sensor array in the vicinity of microneedles.

Claims

1. A microfabricated high-aspect ratio device for delivery of an active agent, comprising a substrate formed of a material selected from the group consisting of metals, ceramics, silicon, glass, polymers, and combinations thereof, wherein the structure is selected from the group consisting of microneedles, microblades, microknives, microchannels and microreservoirs and a combination thereof.

2. The device of claim 1, wherein the metal is titanium, stainless steel, nickel, alloy of nickel-iron, and wherein the polymer is selected from the group consisting of polymethyl methacrylate (PMMA), polyaryletherketone, nylon, PET, poly(lactic acid), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), polycarbonate, polystyrene, and a combination thereof.

3. A microfabricated device as defined in claim 1, additionally comprising at least one skin-contacting area that is connected through microchannels to a reservoir with active agents.

4. A microfabricated device as defined in claim 1, wherein the microfabricated needles or knives or blades are coated with a thin dry reagent formulation that contains active agents for therapeutic applications in treating, preventing, or ameliorating a body condition.

5. A microfabricated device as defined in claim 1, wherein the microfabricated micro-needle is within close vicinity of the biosensor-array for body fluids analysis to determine a body condition.

6. A method of making the microfabricated devices as defined in the claim 1, comprising:

performing a first isotropic etch to define microneedle tips or microknife edge, and

performing a second anisotropic Bosch etch to define microneedle shaft or microknife body.

7. A method of making microfabricated devices as defined in the claim 1, comprising:

performing an anisotropic etch first to define the body of microneedle or microblade and performing orientation dependent etch of Si using potassium hydroxide or tetramethyl ammonium hydroxide or sodium hydroxide solution.

8. A method of making the microfabricated device as defined in the claim 1, comprising moving one or two electrodes selected from the group consisting of a working electrode with materials defined in the claim 2 which is the cathode and the counter electrode which is a patterned anode during electrochemical etch.

9. A method of making the microfabricated device as defined in the claim 1, comprising injection molding or hot embossing using polymer materials defined in the claim 2.

10. A method of using the devices as defined in claim 1 for treating, preventing, or ameliorating a body condition, comprising

pushing a plurality of microneedles through the outer layer of skin or scratching a plurality of microblades or microknives on a preselected site of the skin, and

followed by applying a skin patch containing active agents over the preselected skin site.

11. A method of using the devices as defined in claim 4 for treating, preventing, or ameliorating a body condition, comprising pushing a plurality of microdevices through the outer layer of skin or scratching a plurality of microdevices at a preselected skin site.

12. The method of claims 10 and 1 1, wherein the active agent is a therapeutic agent selected from the group consisting of antibiotics, hormones, steroids, anti-inflammatory drugs, protein drugs, DNA drugs, recombinant Erythropoietin (rhEPO), Taxol®

, Interferon-alpha-1b, Interferon beta, Interferon gamma, Emla®

, Fluorouracil, Lidocaine, Salicylic acid, Pureriran, eflornithine hydrochloride, spironolactone, flutamide, insulin, nanoparticle drugs, Epidural, recombinant human parathyroid hormone, growth hormone, thyroid, cortisol, estrogen, progesterone, and testosterone and combinations thereof.

13. The method of claims 10 and 1 1, wherein the active agent is a cosmetic substance selected from the group consisting of botulinum toxin type A, hyaluronic acid and its derivatives, acetyl hexapeptide-3, vitamin A, vitamin C, vitamin E, alpha-hydroxyacids, collagen and hormones.

14. The method of claims 10 and 1 1, wherein the active agent is selected from the group consisting of vaccines, protein vaccines, peptide vaccines, gene vaccines and DNA vaccines, whether natural or synthesized, against influenza (flu), diphtheria, tetanus, pertussis (DTaP), measles, mumps, rubella (MMR), hepatitis B, polio, haemophilus influenzae type b, chickenpox, tuberculosis, anthrax, yellow fever, rabies, AIDS, cancers, meningococcus, SARS and cholera.

15. The method of claims 10 and 11, wherein the active agent is quantum dots, functionalized nanoparticles, magnetic particles or a combination of thereof for diagnostic purpose.

16. The method of claims 10 and 11, wherein the microdevice performs controlled release of active agent defined in the claims 12, 13, 14 and 15.

17. The method of claim 10, wherein the microdevice performs topical delivery of active agent defined in the claims 12, 13, 14 and 15.

18. The method of claims 10 and 11, wherein body condition is a medical condition and/or cosmetic condition.

19. The method of claim 18, wherein the medical condition is one or plurality of AIDS, breast cancer, melanoma, liver cancer, lung cancer, blood cancer, pituitary tumors, other cancers, flu, infection, blood disease, cardiac disease, back pain, neck pain, body pain, general pain, arthritis, osteoporosis, headache, depression, smoke, alcoholic, overweight and obesity, menopause, facial hair growth, balding, polycystic ovary syndrome, need of inoculation, need of anesthetics and in particular dermal disease.

20. The method of claim 18, wherein the cosmetic condition is one or plurality of skin aging, skin wrinkle, dark spot, skin discoloration, moisturizing, skin lightening, skin whitening, skin firming, skin lifting, acne, wart, infection, irritation, dry skin and oily skin.