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Overview

Introduction

Responsive drug delivery

Sensing

DeliveryMicrofabrication

Telemetry

Future perspectives and challenges

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Introduction

Drug absorption, distribution and metabolism varyamong individuals

Individualized therapy

Controlled releaselow therapeutic index

high patient compliance

Cannot respond individuals drug therapy

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Responsive drug delivery

Located inside patients body-sense-deliver drug

ICD (implantable cardiodefibrillator) monitors heart

beatSensing:

highly sensitive, selective

and robust sensors-monitor

small volumes of body fluids

Protein engineering, molecularbiology-bioreagents-biosensors

Human physiology,physiological fluids- affectbiosensors

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Glucowatch- reverse iontophoresis-interstitial fluid.

Medtronic MiniMed sensor, MiniMeds 2007

implantable insulin pump- 72 hrs Alpha Dx, the OPTI critical care analyser,

the senDX 100, I-Stat point of care bloodanalysis

Advantage of closed loop drug delivery:

life sustaining benefit for cardiac

serve as alarm angina, stroke, cancer,etc

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Limitations:

Biocompatability and foreign bodyresponse

Solutions:

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 usingMEMS size 16X12X1.86mm, flow rate

100 l/h.

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Types of drug delivery systems.

Commercially available

Implantable fusion pumps

Noninvasive reverse ion-

tophoresis devices

Controlled release

Duros implant technology

Responsive

Closed loop

Responsive polymers

Micro and miniaturesystems

Microfabricated sacrificial

valves

Artificial muscle

miniature valves

Main features

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/beneath

the 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 in 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

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Duros controlled releasedevice pain medication

4mm diameter, 44mmlength holds 150L drug

and deliver at rate0.4L/day.

Responsive delivery release physiological signal

Smart polymers deliver

drug biological stimulus

Antigen-antibodyinteraction

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Detection of S. aureus increased thrombinrelease antibiotic gentamicin

Gentamicin bound-PVA hdrogel-peptide linker

Thrombin-Biologically inactiveactive by leucineaminopeptodase

Self-relating insulin delivery devices immobilizingglucose oxidase(GOx) in a pH-sensitive hydrogel

Problems: Passive drug release, nonphysiological working

pH, nonreproducible drug release, slow responsetime, biocompatability and limited lifetimes

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Microfabrication: Nonconventional MEMS polymeric materials

control surface hydrophilicity and minimize protein

absorption 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

Properties of responsive drug delivery device

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 sterilizeand allow high drug loading

Continuous monitoring, telemetric data transfer and allowphysician intervention if needed

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Control- circadian rhythm

Covera-HS hypertension/anginapectoris

Norplant - Subcutaneousimplantationcontraceptive device

Incorporating telemetry accesssensor and delivery at all times.

http://www.bakercountyhealth.org/services/womens-health/photos/norplant.jpg

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