USDA

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USDA Nanotech Delivery of
(Bio)molecules ?
USDA November 18, 2002

• Mauro Ferrari, Ph.D.
• Associate Vice President,
• Health Sciences, Technology and Commercialization
• Edgar C. Hendrickson Professor of Biomedical
  Engineering
• Associate Director,
• Dorothy M. Davis Heart and Lung Research
  Institute
• Professor of Internal Medicine Mechanical
  Engineering
• M.D. student

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From a Drug-Delivery Perspective

• Proposed Analogy
• Smart drug-delivery systems smart delivery of
  nutrients?
• Smart any combination of
• Spatially Directed
• Time-Controlled Release Profile
• Intelligent Control
• Remotely regulated
• Pre-programmed
• Self-regulated

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En route to self-regulated.

• Integration of
• Sensing of target trigger
• Intelligence onboard
• Release technology
• on delivery implant or particulates for oral,
  intravascular, transdermal or aerosol delivery

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Crucial Bottlenecks

• Stability of Implanted Sensing Technology To
  Develop Antifouling Tech, or Fouling-Insensitive
  Strategies?
• Availability of Appropriate Disease Markers
• (On-board Logics Linkage Between Sensing and
  Therapeutic Delivery)
• SMART DELIVERY TECHNOLOGY

From NIH BECONs Active Disease Management,
6/25/02
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Three examples of use of (top-down)
nanotech

• Nanopores for controlled release of biomolecules
• Nanopores for immunoprotected implantation of
  cell bioreactors
• Multifunctional particles for the oral delivery
  of biological molecules
• (from my lab and iMEDD, Inc please note that I
  have a financial interest in iMEDD)

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NanoPORE Fabrication Process
Silicon Wafer
Etch Trenches
Deposit Sacrificial Oxide Layer
Deposit Poly Silicon Structural Layer
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NanoPORE Fabrication Process
Planarized
Apply Etch Stop
Back Etch
Remove Etch Stop
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NanoPORE Fabrication Process
Remove Sacrificial Oxide
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NanoPORE Fabrication Process
Array of NanoPORE Channels
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NanoPUMP Implantable Drug Delivery Device
Nanopore membrane array
Switch (open)
Check valve (closed)
Vent
Cathode
Release orifice
Anode
Plunger
Battery pack
Iso-osmotic electrolyte primer solution
Drug/electrolyte solution
Biocompatible encasement
Switch (closed)
Check valve (opened)
Advancing Plunger
Vent
Released Drug
Drug/electrolyte solution
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NanoPORE Array
Top View
Pore
Anchor
Poly Silicon Beam
SEM showing top views of parallel 50 nanometer
pores (each 45 mm long)
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NanoPORE Array
Cross Section View
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NanoGATE Glucose Diffusion
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Albumin Diffusion Kinetics
Cumulative Percent Release
Time (Days)
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Robotic surgery meets nanotech
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BIOCAPSULE/1History of Cell Encapsulation

• Active research field for over three decades
• Previous focus has been entirely on natural or
  synthetic polymeric biocapsules Chang, 1967
  Lim Sun, 1980 Lacy, 1991 Lanza, 1992
  Soon-Shiong, 1993 Scharp Hubbell and
  many more...

• Limitations associated with premature
  biodegradation, chemical and mechanical
  instability, and broad pore size distributions

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Cell Transplant Biocapsule

• Implant containing cells to produce insulin (or
  other therapeutic agent)
• Membrane protects transplanted cells from immune
  attack
• Phase 2 SBIR Grant application

Figure 8. IgG Diffusion into biocapsule
Figure 11. Non fasting blood glucose
concentration and body weight in STZ-diabetic
Lewis rat after biocapsule implantation
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Starting with oral..
The Programmable Pill By Alexandra
Stikeman Technology Review May 2001 Vol.
104/No.4, pp.78-83
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Oral Peptide DeliveryTransport through the GI
Tract
Capsule dissolves in intestines releasing
drug-loaded particles
Enteric coating protects drug-loaded particles in
acidic stomach
Particles adhere to intestinal wall and transport
contents into the blood stream
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Anatomy of Intestinal Mucosa
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Intestinal Mucosa Tight Junction Complex
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Microfabricated Porous Silicon Particles
(b) Released Particle
(a) Particles on Substrate
Size 150 300 ?m Thick 25 ?m Pore Size 20
100 nm Porosity 70
(c) Pores in Particle
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Porous Silicon Particles
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Porous Silicon Particles
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For Delivery of Biologically Active Peptides and
Proteins
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Relative Size of Trans-Mucosal Patch
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Oral MEDDS Particles
Enhanced Transport of Insulin CACO-2 Intestinal
Model
(22)
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( of dose/hr)
Transport of Insulin
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(2)
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Control
OralMEDDS Particles
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Strategy Need FACILITIES
Science Village at Ohio State MicroMD First
Dedicated bioMEMS/Nanotechnology RD Facility
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Thanks

• Ferrari.5_at_osu.edu