1. Responsive Drug Delivery System
Presenter:
Bo He
12/10/03

2. Outline
Traditional drug dosing & introduction to responsive drug delivery systems
Commercially available sensors & drug delivery systems
Responsive drug delivery systems under development
Challenge & perspective
A commercially available responsive drug delivery system – insulin pumps

3. Traditional Drug Dosing
Medicine or injections
Each person responds uniquely
Noticeable symptoms are not sufficient to support timely and accurate dosing
Examples- diabetes, cardiovascular disease, acute pain
Controlled release – frequent exposure, side effects, tolerance
Drug absorption, distribution, and metabolism can vary widely among individuals, even within the same family.
It’s hard to predict when the heart stroke will happen.
Unpredictable absorption of injected insulin can give you unpredictable blood sugar level.

4. Responsive Drug Delivery Systems
Combination of Biosensors & controlled release system
Revolutionized medicine by enabling individualized therapy
Sense continuously to manage unpredictable condition
Immediate respond with appropriate countermeasure
Give the patients more flexibility and less disruption of the daily life

5. Example: Insulin Pumps
An insulin reservoir (like a regular syringe)
A small battery operated pump
A computer chip for control
Infusion set- a thin plastic tube to deliver insulin to the body
Pump therapy
A basal rate & bolus insulin
Combination with Glucose sensors
Reservoir and pump are incorporated in a plastic case about the size of a beeper.

6. The Importance of Control
Programmed release controlled by microchips
More flexibility & less pain
Reduced the risk of side effects
More than 200,000 people in the US wear insulin pumps
Predictable blood sugars
Flexible meal intake, go sports, no multiple shots every day.

7. Ideal Responsive Drug Delivery
Disadvantages of available systems
Not automatic, the user has to decide the dose
The results are not always reliable
Sensors and controlled drug delivery systems are not combined
Ideal systems
Sense minute amounts of marker molecules
Immediate response
In vivo detection and delivery
Small, biocompatible, accurate and reproducible
Biomolecule acting
In vivo detection and delivery provides immediate response with minimal disruption to the patient’s daily life.

8. Type of Drug Delivery Commercially available Responsive
Noninvasive reverse iontophoresis devices
Implantable fusion pumps
Duros implant technology controlled release
Responsive
Closed loop
Smart polymers

9. Biosensors, e.g. Glucowatch
Biographer: non-invasive, watch-like device that measures glucose
AutoSensor: a plastic part that snaps into the Biographer and sticks to the skin.
Noninvasive & automatic reading every 10 mins up to 13h

10. Comparison of Glucose Readings

11. How does Glucowatch work?
Based on reverse iontophoresis
A low electric current pulls glucose through the skin. Glucose is accumulated in two gel collection discs in the AutoSensor.
Another electrode in the AutoSensor measures the glucose.

12. Enzymatic pathway
Glucose oxidase catalyze oxidization of glucose in hydrogel
Hydrogen peroxide reacts on the platinum electrode, providing electrons
Current is proportional to glucose

13. Controlled-release device
Affecting factors
Compositions of osmotic agent
Thickness of semipermeable membrane
Surface area

14. Responsive drug delivery systems
Smart polymer
Antigen-antibody interaction
Closed loop systems
Sensing and delivery combo system

15. Antigen-antibody interaction smart polymers
A semi-interpenetrating polyacrylamide (PAAm) hydrogel
Antigen—rabbit immunoglobulin G( rabbit IgG)
Antibody—goat anti-rabbit IgG (GAR IgG)
Takashi Miyata et al., Nature, vol 399 ,766

16. Antigen-antibody interaction smart polymers
Effect of free antigen concentration on the hydrogen swelling ration
Antigen recognition by antigen-antibody semi-IPN hydrogel

17. Antigen-antibody interaction smart polymers
Reversible swelling changes
Antigen-responsive permeation
(a model protein drug haemoglobin through a membrane fabricated from hydrogel )

18. Schematic of Self Regulating Responsive Therapeutic System

19. Challenge Commercially available systems Systems under development
Expensive yet not always reliable
Not automatically responsive
Not completely in vivo
Systems under development
Short lifetime and hard to reproduce
Slow response time
Biocompatibility (coating)
Coating
Passive drug release at physiological glucose levels

20. References Sapna K. Deo; et al. Analytical Chem. 2003, 206A-213A.
R. T. Kurnik et al. Electrochem. Soc. 1998, 145,
Miyata, T. et al. Nature 1999, 399, 766–769.
Zhang, K.; Wu, X. Y. J. Controlled Release 2002, 80, 169–178.
Tanihara, M. et al. J. Pharm. Sci. 1999, 88, 510–514.
Metzger, M. et al. Diabetes Care 2002, 25, 1185–1191.

21. Thank You