Responsive Drug Delivery SystemsApplying micromachining, biosensors, telemetry, andother techniques at the interface of analytical chemistryand bioengineering to revolutionize drug delivery. :Responsive Drug Delivery SystemsApplying micromachining, biosensors, telemetry, andother techniques at the interface of analytical chemistryand 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 Mohana Marimuthu 200840090


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


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


Responsive drug delivery :Responsive drug delivery Located inside patient’s body- sense-deliver drug ICD (implantable cardio defibrillator) – 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


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


Slide 6:Limitations: Biocompatability and foreign body response Solutions: use of biomimetic surfaces, polyethylene oxide coatings, NO – releasing material Delivery: 2 types of commercial delivery system 1. implantable infusion pump 2. noninvasive reverse iontophoretic devices Piezo actuated silicon micropump using MEMS – size 16X12X1.86mm, flow rate – 100 µl/h.


Slide 7: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 miniature systems 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 microvial’s lid Based on a soft hydrogel and polymer blend that mimics natural muscle functions


Slide 8:Duros – controlled release device – pain medication 4mm diameter, 44mm length holds 150µL drug and deliver at rate 0.4µL/day. Responsive delivery release – physiological signal Smart polymers – deliver drug – biological stimulus Antigen-antibody interaction


Slide 9:Detection of S. 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, nonphysiological working pH, nonreproducible drug release, slow response time, biocompatability and limited lifetimes


Slide 11: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


Slide 13:Telemetry Wireless transmission of data Integrated with defibrillators, pumps or retinal prosthetics Monitor – intrauterine pressure changes,body temperature and heart rate of a fetus Pill sized wireless cameras and image sensors – endoscopic capsules


Future perspectives and challenges :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 sterilize and allow high drug loading Continuous monitoring, telemetric data transfer and allow physician intervention if needed


Slide 16:Control- circadian rhythm Covera-HS – hypertension/angina pectoris Norplant - Subcutaneous implantation –contraceptive device Incorporating telemetry – access – sensor and delivery at all times.


Slide 17:Thank you