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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

Presenter:

Bo He

12/10/03


Outline l.jpg
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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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


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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


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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


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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


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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



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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



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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.


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Enzymatic pathway

  • Glucose oxidase catalyze oxidization of glucose in hydrogel

  • Hydrogen peroxide reacts on the platinum electrode, providing electrons

  • Current is proportional to glucose


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Controlled-release device

  • Affecting factors

    • Compositions of osmotic agent

    • Thickness of semipermeable membrane

    • Surface area


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Responsive drug delivery systems

  • Smart polymer

    • Antigen-antibody interaction

  • Closed loop systems

    • Sensing and delivery combo system


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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


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Antigen-antibody interaction smart polymers

Effect of free antigen concentration on the hydrogen swelling ration

Antigen recognition by antigen-antibody semi-IPN hydrogel


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Antigen-antibody interaction smart polymers

  • Reversible swelling changes

  • Antigen-responsive permeation

  • (a model protein drug haemoglobin through a membrane fabricated from hydrogel )



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Challenge

  • 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)


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References

  • 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.



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