Biosensors_Lecture10

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Responsive Drug DeliverySystems

Lecture 10

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 System

Applying micromachining, biosensors, telemetry, and

other techniques at the interface of analytical

chemistry and bioengineering to revolutionize drug

delivery

Responsive drug delivery:

SensingDelivery

Micro-fabrication

Telemetry

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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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ICD (implantable cardio defibrillator)

Located inside patients body-

sense-deliver drug

Monitors heart beat

Sensing:

highly sensitive, selective

and robust sensors-monitor

small volumes of body fluids

Protein engineering, molecular

biology-bioreagents-biosensors

Human physiology, physiological

fluids- affect biosensors

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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 Glucosesensors

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Glucowatch

Reverse iontophoresis (a.k.a.

Electromotive Drug Administration

(EMDA))- interstitial fluid.

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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Comparison of Glucose Readings

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Advantage of closed loop drug delivery:

life sustaining benefit for cardiac

serve as alarm angina, stroke, cancer, etc

Alpha Dx, the OPTI critical care analyser, the senDX

100, I-Stat point of care blood analysis

Medtronic MiniMed sensor, MiniMeds 2007

implantable insulin pump- 72 hrs

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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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Limitations: Biocompatability and foreign body

responseSolutions: use of biomimetic surfaces,

polyethylene oxide coatings,NO releasing material

Delivery: 2 types of commercial delivery system

1. implantable infusion pump2. noninvasive reverse iontophoretic

devices Piezo actuated silicon micropump using

MEMS size 16X12X1.86mm, flow rate 100 l/h.

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Types of responsive drug delivery systems

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Commercially available

Implantable fusion pumps

Noninvasive reverse ion-tophoresis devices

Controlled release

Duros implant technology

Responsive

Closed loop

Responsive polymers

Micro and miniature

systems

Microfabricated sacrificial

valves

Artificial muscle

miniature valves

Preprogrammed to deliver at any release rate through a catheter to a

specific body location

Electric current applied across skin to extract analyte from within/beneaththe skin

Continuous release for pain medication, individually tailored using an

osmotic gradient

Delivers as a function of sensor signal;includes sensing and release systems

Release from a smart polymer i n response to a stimulus

Contains nano- to low-microliter volumes of therapeutic agents in

individually sealed reservoirs; drug is released by electrochemically

removing each microvials lid

Based on a soft hydrogel and polymer blend

that mimics natural muscle functions

Duros controlled release device

Pain medication

4mm diameter, 44mm

length holds 150L drug

and deliver at rate

0.4L/day.

Responsive delivery

release physiologicalsignal

Smart polymers deliver

drug biological stimulus

Antigen-antibody

interaction

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Controlled-release device

Affecting factors:

Compositions of osmotic agent

Thickness of semipermeable membrane

Surface area

Antigen-antibody interaction smart polymers

A semi-interpenetrating

polyacrylamide (PAAm)

hydrogel

Antigenrabbit

immunoglobulin G

(rabbit IgG)

Antibodygoat anti-

rabbit IgG (GAR IgG)

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Effect of free antigen concentration on the

hydrogen swelling rationAntigen recognition by antigen-antibody

semi-IPN hydrogel

Takashi Miyata et al., Nature, vol 399 ,766


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Reversible swelling

changes

Antigen-responsive

permeation

(a model protein

drug haemoglobin

through a membrane

fabricated from

hydrogel )

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Schematic of a Self Regulating

Responsive Therapeutic System

Microfabrication:

Nonconventional MEMS polymeric materials

control surface properties

Microreservoirs store sensing reagents/active drug

solid or liquid form

Eg. Microchip based device mechanism -

elecrochemical dissolution of metal cover film Soft hydrogel and polymer valves

-mimic natural muscle

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Telemetry

Wireless transmission of data

Integrated with defibrillators, pumps or retinalprosthetics

Monitor intrauterine pressure changes, bodytemperature and heart rate of a fetus

Pill sized wireless cameras and image sensorsendoscopic capsules

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Future perspectives and challenges

Combination of sensing and delivery

Small and easy to implant and remove, patient

compliance

Long-lived, biocompatible and inexpensive

Inert, mechanically strong, comfortable for patient

Safe from accidental release, easy to fabricate and

sterilize and allow high drug loading

Continuous monitoring, telemetric data transfer and

allow physician intervention if needed

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Control- circadian rhythm

Norplant - Subcutaneous

implantation contraceptive

device

Incorporating telemetry

access sensor and delivery at

all times.

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Documents

Biosensors_Lecture10