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Responsive Drug Delivery Systems

Applying micromachining, biosensors, telemetry, and other techniques at the interface of analytical chemistry and bioengineering to revolutionize drug delivery.

Sapna K. Deo, Elissavet A. Moschou, Serban F. Peteu, Leonidas G. Bachas, Sylvia Daunert - University of Kentucky Patricia E. Eisenhardt, ChipRx, Marc J. Madou - University of California – Irvine

Akbari Abolfazl nanolife

Overview    Introduction Responsive drug delivery Sensing Delivery Microfabrication Telemetry Future perspectives and challenges .

distribution and metabolism vary among individuals Individualized therapy Controlled release low therapeutic index high patient compliance Cannot respond – individuals drug therapy .Introduction     Drug absorption.

molecular biology-bioreagents-biosensors  Human physiology.Responsive drug delivery Located inside patient’s bodysense-deliver drug  ICD (implantable cardio defibrillator) – monitors heart beat Sensing:  highly sensitive.affect biosensors  . selective and robust sensors-monitor small volumes of body fluids  Protein engineering. physiological fluids.

Glucowatch. etc  . the OPTI critical care analyser. I-Stat point of care blood analysis Advantage of closed loop drug delivery:  life sustaining benefit for cardiac  serve as alarm – angina. cancer. the senDX 100. MiniMed’s 2007 implantable insulin pump.reverse iontophoresisinterstitial fluid.  Medtronic MiniMed sensor.72 hrs  Alpha Dx. stroke.

86mm. implantable infusion pump 2. polyethylene oxide coatings.Limitations:  Biocompatability and foreign body response Solutions:  use of biomimetic surfaces. flow rate – 100 µl/h. noninvasive reverse iontophoretic devices  Piezo actuated silicon micropump using MEMS – size 16X12X1. . NO – releasing material Delivery:  2 types of commercial delivery system 1.

Main features Commercially available Implantable fusion pumps Noninvasive reverse iontophoresis devices Controlled release Duros implant technology Responsive Closed loop 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.Types of drug delivery systems. individually tailored using an osmotic gradient Delivers as a function of sensor low-microliter volumes of therapeutic agents in valves individually sealed reservoirs. drug is released by electrochemically removing each microvial’s lid “Artificial muscle” Based on a soft hydrogel and polymer blend miniature valves that mimics natural muscle functions .includes sensing and release systems Responsive polymers Release from a smart polymer in response to a stimulus Micro and miniature systems Microfabricated “sacrificial” Contains nano.

4µL/day. 44mm length holds 150µL drug and deliver at rate 0. Responsive delivery release – physiological signal Smart polymers – deliver drug – biological stimulus Antigen-antibody interaction .     Duros – controlled release device – pain medication 4mm diameter.

nonphysiological working pH. nonreproducible drug release. aureus – increased thrombin – release antibiotic gentamicin  Gentamicin bound-PVA hdrogel-peptide linker  Thrombin-Biologically inactive–active by leucine aminopeptodase  Self-relating insulin delivery devices – immobilizing glucose oxidase(GOx) in a pH-sensitive hydrogel Problems:  Passive drug release. slow response time. biocompatability and limited lifetimes  .Detection of S.


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 .


body temperature and heart rate of a fetus  Pill sized wireless cameras and image sensors – endoscopic capsules .Telemetry  Wireless transmission of data  Integrated with defibrillators. pumps or retinal prosthetics  Monitor – intrauterine pressure changes.

easy to fabricate and sterilize and allow high drug loading  Continuous monitoring.Future perspectives and challenges Properties of responsive drug delivery device  Combination of sensing and delivery  Small and easy to implant and remove. Biocompatible and inexpensive  Inert. mechanically strong. comfortable for patient  Safe from accidental release. patient compliance  Long-lived. telemetric data transfer and allow physician intervention if needed .


.Subcutaneous implantation –contraceptive device Incorporating telemetry – access – sensor and delivery at all times.circadian rhythm Covera-HS – hypertension/angina pectoris Norplant .    Control.