Therapeutic microdevices and methods of making and using same

• US 6,107,102 A
• Filed: 08/07/1997
• Issued: 08/22/2000
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: California Polytechnic State University (California State University System)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Ferrari, Mauro
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Hines, Jana A.
• Application Number:
  US08/908,334
• Time in Patent Office: 1,111 Days
• Field of Search: 424/9.1, 424/9.2, 424/9.3, 424/9.32, 424/9.321, 424/9.322, 424/9.34, 424/9.341, 424/417, 424/422, 424/426, 424/450, 424/181.1, 424/811, 424/812, 427/2.14, 427/213.3, 435/182, 436/518, 436/525, 436/64, 436/73, 436/829, 604/891.1, 604/48, 604/57
• US Class Current: 436/518
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61K 49/04 X-ray contrast preparations
• CPC Class Codes: A61K 49/18 characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
• CPC Class Codes: A61K 49/222 characterised by a special physical form, e.g. emulsions, liposomes
• CPC Class Codes: A61K 51/1282 Devices used in vivo and carrying the radioactive therapeutic or diagnostic agent, therapeutic or in vivo diagnostic kits, stents
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/51 Nanocapsules; Nanoparticles; nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: Y10S 424/811 involving sex selection or contraception
• CPC Class Codes: Y10S 424/812 Liposome comprising an antibody, antibody fragment, antigen, or other specific or nonspecific immunoeffector

Abstract

A suspension of microfabricated microdevices for use in therapeutic applications is disclosed. The microdevices have a selected shape, and uniform dimensions preferably in the 100 nm to 10 Am range. Also disclosed are microfabrication methods for making such microdevices.

Claims

1. A suspension of microdevices for use in delivering a therapeutic compound to the interstitial space of a target region which is characterized by a target-specific marker on a basement membrane forming a vasculature of the target region, comprising

a suspension of microdevices in an aqueous medium, said microdevices (i) having a selected non-spherical shape, uniform dimensions and a selected maximum dimension in a range of 0.1 and 3 microns and (ii) composed of at least two separate bodies, including a support having at least one planar surface, and a therapeutic agent attached to the support, said therapeutic agent being in a form such that the activity of the therapeutic agent is expressed in direct response to a chemical or biochemical interaction that occurs upon exposure of the microdevice to a biochemical environment of a target site after administration of the microdevices to a subject, said microdevices containing a surface-bound marker-binding molecule effective to bind to such marker, and an enzyme effective to lyse the basement membrane.

2. The suspension of claim 1, wherein said enzyme is a type IV collagenase.

3. The suspension of claim 1, wherein said enzyme is covalently attached to a surface region of the microdevices.

4. The suspension of claim 1, wherein said enzyme is contained in said microdevices in releasable form, and the enzyme is released from said microdevices upon microdevice bioerosion.

5. A suspension of microdevices for use in administering a therapeutic agent to a selected target site in a subject, comprising

a suspension of microdevices in an aqueous medium, said microdevices (i) having a selected non-spherical shape and uniform dimensions and (ii) composed of at least two separate bodies, including a support having at least one planar surface, and a therapeutic agent attached to the support, said therapeutic agent being in a form such that an activity of the therapeutic agent is expressed in direct response to a chemical or biochemical interaction that occurs upon exposure of the microdevice to a biochemical environment of the target site after administration of the microdevices to the subject, wherein the microdevices are substantially disc-shaped, and have a laminated structure containing first and second disc-shaped layers forming said support and therapeutic agent, respectively.

6. The suspension of claim 5, wherein the microdevices have a trilaminate structure composed of an interior layer forming said therapeutic agent sandwiched between a pair of exterior coating layers at least one of which forms said support, and the coating layers have a slower rate of bioerosion than the interior layer.

7. A suspension of microdevices for use in administering a therapeutic agent to a selected target site in a subject, comprising

a suspension of microdevices in an aqueous medium, said microdevices (i) having a selected non-spherical shape and uniform dimensions and (ii) composed of at least two separate bodies, including a support having at least one planar surface, and a therapeutic agent attached to the support, said therapeutic agent being in a form such that an activity of the therapeutic agent is expressed in direct response to a chemical or biochemical interaction that occurs upon exposure of the microdevice to a biochemical environment of the target site after administration of the microdevices to the subject, wherein the microdevices have substantially disk-shaped supports having radially-disposed regions which contain said therapeutic agent.