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Responsive Drug Delivery System. Presenter: Bo He 12/10/03. Outline. Traditional drug dosing & introduction to responsive drug delivery systems Commercially available sensors & drug delivery systems Responsive drug delivery systems under development Challenge & perspective.

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responsive drug delivery system

Responsive Drug Delivery System


Bo He


  • 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
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
responsive drug delivery systems
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
example insulin pumps
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
the importance of control
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
ideal responsive drug delivery
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
biosensors e g glucowatch
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
how does glucowatch work
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.
enzymatic pathway
Enzymatic pathway
  • 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
Controlled-release device
  • Affecting factors
    • Compositions of osmotic agent
    • Thickness of semipermeable membrane
    • Surface area
responsive drug delivery systems14
Responsive drug delivery systems
  • Smart polymer
    • Antigen-antibody interaction
  • Closed loop systems
    • Sensing and delivery combo system
antigen antibody interaction smart polymers
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 polymers16
Antigen-antibody interaction smart polymers

Effect of free antigen concentration on the hydrogen swelling ration

Antigen recognition by antigen-antibody semi-IPN hydrogel

antigen antibody interaction smart polymers17
Antigen-antibody interaction smart polymers
  • Reversible swelling changes
  • Antigen-responsive permeation
  • (a model protein drug haemoglobin through a membrane fabricated from hydrogel )
  • Commercially available systems
    • 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)
  • Sapna K. Deo; et al. Analytical Chem. 2003, 206A-213A.
  • 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.
  • Metzger, M. et al. Diabetes Care 2002, 25, 1185–1191.