Chemically Responsive Drug Delivery Implant with Refill Capacity

1
Chemically Responsive Drug Delivery Implant with
Refill Capacity

• Bio-E 121 Final Project
• Calvin Chen
• Stanley Lee

2
Overview

• Background Information
• Current technology
• Improvements with miniaturization
• Design of New Chip
• Schematics
• Mechanisms
• Fabrication
• Applications Diabetes
• Conclusion

3
Background Information

• Current Technology for Drug Delivery
• Injections
• Pills
• Macroscopic drug delivery systems
• Biodegradable Injected Systems (nanoshells)
• Epidermal patches
• Inhalants
• Needleless injection
• (gas burst)

4

• Problems With Current Systems
• Inconsistent drug levels over time
• Big and bulky implantable systems
• Forget to take pills (birth control)
• Inconvenient visits to the doctor
• Infection or spotting from multiple injections

5
Improvements with Miniaturization

• Controlled drug flow
• Active system adapts to changing body conditions
• Faster delivery
• Reduced power consumption
• Less moving parts
• Site specific delivery reduces side effects
• Cheaper

6
Hydrogels

• Water swollen 3-D cross-linked network of
  hydrophilic polymers
• Environmentally sensitive polymer gels
• Different chemical composition determines
  response to pH, temperature, electric field,
  light, carbohydrates, antigens, or proteins
• Polymer network exhibits volume change response
• Considered to be the most efficient polymer
  system in transforming molecular energy into
  mechanical force

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Why use hydrogel?

• Advantages
• No power required
• No wear or friction by moving parts
• Adaptable to different stimuli
• Easily fabricated, without clean room
• Large force generation and displacement

8
Hydrogel Actuation (pH response)

• As pH varies, the networks become charged by
  protonation of amine groups or deprotonation of
  acid groups
• Repulsion of like charges collapse hydrogen bonds
  at high pH levels and cause network to expand and
  fill with water, resulting in volume change and
  vice versa

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Hydrogel Valve Implementation

• pH sensitive hydrogel consists of 2-hydroxyethyl
  methacrylate (HEMA) and acrylic acid in a 41
  ratio, ethylene glycol dimethacrylate (EGDMA) and
  Irgacure 651 before UV polymerization
• pH insensitive hydrogel consists of HEMA, EGDMA
  and Irgacure 651 before UV polymerization
• Backward flow negligible

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Hydrogel Characterization
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The Refill Port

• The refill port of chip will be slightly raised
  so it can be felt through the skin
• Silicone rubber septum is biocompatible and
  self-sealing
• Implant is located in abdomen where there is
  sufficient tissue for support to prevent movement
  during refill
• Need a way to determine when the chip needs to be
  refilled
• Stainless steel needle stop lines refill port to
  prevent damage/puncture of chip during refill

12
Chip Design
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• major axis 2 in.
• minor axis 1.5 in.
• Height 0.5 in.

Total reservoir volume 3-5 mL
14
Material Selection

• Biocompatibility concerns
• Device cannot corrode
• Cannot react with drug to produce toxic side
  products
• Long life
• Proposed Materials
• Polymers (PMMA, PDMS, Teflon, Polyethylene etc.)
• Titanium
• Glass
• Silicon

15
Fabrication

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Example Application Type I Diabetes

• Kinetics of injection administered drug does not
  mimic natural body insulin secretion response
• Near the pH sensing area of the hydrogel, glucose
  oxidase/catalase can be applied, which reacts
  with glucose in the blood to alter the pH level
  in that area.
• High glucose concentration leads to lower pH
  levels, low glucose concentration leads to higher
  pH levels.

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Drawbacks of System

• Need to test for leakage
• Although fatigue is minimal, its still present
  in the hydrogels and reservoir
• Somewhat imprecise dosages
• Because of small size, capacity is limited
• Need to test release rate/long period of time
  (constant flow rate)
• Hydrogel swelling can be slow

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The Future of Drug Delivery

• Future improvements will allow chip to be applied
  to more challenging disease treatments
• Site specific delivery by catheter so
  concentration of drug is high only where needed
• Advanced diseases that will be treated
• chronic pain
• Parkinsons and Alzheimers disease
• Deliver treatment neurotransmitters past
  blood-brain barrier
• antibiotic delivery
• Insoluble drugs have to be mixed with chaotic
  flow fields
• hormone treatments