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Responsive Drug Delivery System

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

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  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

  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

  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

  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

  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

  8. Type of Drug Delivery

  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 • 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)

  20. 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.

  21. Thank You

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