This document discusses the development of smart glucose responsive biodegradable polymers for insulin delivery. It notes that 350 million people have diabetes worldwide and current therapies do not tightly control blood sugar. It then describes the development of a glucose-responsive particle system that degrades in response to glucose to release insulin on demand over several hours, reducing risks of overdose and the need for frequent injections. The system aims to more closely mimic natural insulin release for improved diabetes treatment.

1. Smart glucose responsive biodegradable
polymers for insulin delivery
Benjamin Tang
JDRF - New England
April 10, 2012

2. 350 million affected by diabetes in 2011
International Diabetes Foundation Atlas Fifth Ed.
• By 2030, 550 million are expected to have diabetes
• 4.6 million deaths in 2011
• Type 2 diabetes accounts for 90%
• Type 1 diabetes increasing 5% annually

3. Current T1D therapies are intensive and do
not tightly control blood sugar
Shaded area - normal healthy range
Dotted lines - insulin replacement therapy
Jacobs Diabetes Care 1997

4. Closed loop insulin delivery for T1D
Measure blood glucose
Insulin delivery
system
Deliver appropriate insulin dose
Continuously monitor to tightly control blood glucose

5. Closed loop insulin delivery systems
Continuous glucose monitor & insulin pump
• Frequent calibration (daily) and sensor
replacement (3-7 days)
• ~15 min lag time
Implanted glucose monitor and pump
• Shorter lag time (3 min)
• Longer term solution: 1-5 years
Glucose responsive gels
• Combined sensing and delivery
• Material removal after insulin consumed

6. Smart insulin delivery systems
Rapidly deliver required dose of insulin when needed
• Tightly maintain blood glucose within healthy range
• Do not cause hypoglycemic events
Deliver insulin over a long period
• Reduce frequency of injection
• Increase patient compliance
Repeated and easy administration
• No buildup of material in the body
• Composed of biocompatible and safe materials

7. Glucose-degradable particles for insulin
delivery
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Glucose-degradable I
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particle I
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Glucose
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I Insulin I I
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No buildup of particles through repeated injections

8. Glucose-specific particle degradation
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I I I I Gluconic acid
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Glucose-specific enzyme
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High glucose degrades material faster to release more insulin

9. Glucose-dependent drug release
from injectable particles
70
200 mg/dL glucose
60
Total drug released (%)
50
40
30
20
10 Control
0
0 2 4 6 8
Hours
Drug released in a glucose dependent manner
Provides long-lasting and fast-acting insulin dosages

10. Glucose-degradable system
for insulin delivery
Deliver insulin in glucose-dependent manner
• Insulin is delivered on demand
• Reduces risk of insulin overdose (hypoglycemia)
Release insulin through polymer degradation
• No buildup of material for repeated injection
• Degrades into non-toxic byproducts
Deliver insulin for over 7 hours
• Reduces frequency of injection

11. Thank you
Prof. Robert Langer
Prof. Daniel Anderson
JDRF Postdoctoral Fellowship
Leona M. and Harry B. Helmsley Charitable Trust