Transcript Responsive Drug Delivery System

Responsive Drug
Delivery System
Presenter:
Bo He
12/10/03
Outline
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Traditional drug dosing & introduction to
responsive drug delivery systems
Commercially available sensors & drug
delivery systems
Responsive drug delivery systems under
development
Challenge & perspective
Traditional Drug Dosing
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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
Responsive Drug Delivery Systems
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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
Example: Insulin Pumps
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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
The Importance of Control
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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
Ideal Responsive Drug Delivery
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Disadvantages of available systems
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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
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Sense minute amounts of marker molecules
Immediate response
In vivo detection and delivery
Small, biocompatible, accurate and
reproducible
Type of Drug Delivery
Noninvasive reverse iontophoresis devices
Commercially
available
Implantable fusion pumps
Duros implant technology controlled release
Closed loop
Responsive
Smart polymers
Biosensors, e.g. Glucowatch
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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
Comparison of Glucose Readings
How does Glucowatch work?
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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.
Enzymatic pathway
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Glucose oxidase
catalyze oxidization of
glucose in hydrogel
Hydrogen peroxide
reacts on the platinum
electrode, providing
electrons
Current is proportional
to glucose
Controlled-release device
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Affecting factors
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Compositions of osmotic agent
Thickness of semipermeable membrane
Surface area
Responsive drug delivery systems
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Smart polymer
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Antigen-antibody interaction
Closed loop systems
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Sensing and delivery combo system
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
Antigen-antibody interaction smart
polymers
Effect of free antigen concentration
on the hydrogen swelling ration
Antigen recognition by antigenantibody semi-IPN hydrogel
Antigen-antibody interaction smart
polymers
• Reversible swelling
changes
•Antigen-responsive
permeation
(a model protein drug
haemoglobin through a
membrane fabricated
from hydrogel )
Schematic of Self Regulating
Responsive Therapeutic System
Challenge
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Commercially available systems
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Expensive yet not always reliable
Not automatically responsive
Not completely in vivo
Systems under development
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Short lifetime and hard to reproduce
Slow response time
Biocompatibility (coating)
References
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Sapna K. Deo; et al. Analytical Chem. 2003, 206A-213A.
www.minimed.com
www.glucowatch.com
R. T. Kurnik et al. Electrochem. Soc. 1998, 145, 4119-4125
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.
www.chiprx.com
www.acs.ohio-state.edu/unit/research/archive/muscles.htm
Metzger, M. et al. Diabetes Care 2002, 25, 1185–1191.
Thank You