Present study is looking at the problem of integrating drug delivery microcapsule, a bio-sensor, and a control mechanism into a biomedical drug delivery system. A wide range of medical practices from cancer therapy to gastroenterological treatments can benefit from such novel bio-system. Drug release in our drug delivery system is achieved by electrochemically actuating an array of polymeric valves on a set of drug reservoirs. The valves are bi-layer structures, made in the shape of a flap hinged on one side to a valve seat, and consisting of thin films of evaporated gold and electrochemically deposited polypyrrole (PPy). These thin PPy(DBS) bi-layer flaps cover access holes of underlying chambers micromachined in a silicon substrate. Chromium and polyimide layers are applied to implement "differential adhesion" to obtain a voltage induced deflection of the bilayer away from the drug reservoir. The Cr is an adhesion-promoting layer, which is used to strongly bind the gold layer down to the substrate, whereas the gold adheres weakly to polyimide. Drug actives (dry or wet) were pre-stored in the chambers and their release is achieved upon the application of a small bias (~ 1V). Negative voltage causes cation adsorption and volume change in PPy film. This translates into the bending of the PPy/Au bi-layer actuator and release of the drug from reservoirs. This design of the drug delivery module is miniaturized to the dimensions of 200μm valve diameter. Galvanostatic and potentiostatic PPy deposition methods were compared, and potentiostatic deposition method yields film of more uniform thickness. PPy deposition experiments with various pyrrole and NaDBS concentrations were also performed. Glucose biosensor based on glucose oxidase (GOx) embedded in the PPy matrix during elechtrochemical deposition was manufactured and successfully tested. Multiple-drug pulsatile release and continuous linear release patterns can be implemented by controlling the operation of an array of valves. Varying amounts of drugs, together with more complex controlling strategies would allow creation of more complex drug delivery patterns.
This work presents manufacturing and testing of a closed-loop drug delivery system where drug release is achieved by an electrochemical actuation of an array of polymeric valves on a set of drug reservoirs. The valves are based on bi-layer structures made of polypyrrole/gold in the shape of a flap that is hinged on one side of a valve seat. Drugs stored in the underlying chambers are released by bending the bi-layer flaps back with a small applied bias. These polymeric valves simultaneously function as both drug release components and biological/chemical sensors responding to a specific biological or environmental stimulus. The sensors may send signals to the control module to realize closed-loop control of the drug release. In this study a glucose sensor has been integrated with the polymeric actuators through immobilization of glucose oxidase(GOx) within polypyrrole(PPy) valves. Sensitivities per unit area of the integrated glucose sensor have been measured and compared before and after the actuation of the sensor/actuator PPy/DBS/GOx film. Other sensing parameters such as linear range and response time were discussed as well. Using an array of these sensor/actuator cells, the amount of released drug, e.g. insulin, can be precisely controlled according to the surrounding glucose concentration detected by the glucose sensor. Activation of these reservoirs can be triggered either by the signal from the sensor, or by the signal from the operator. This approach also serves as the initial step to use the proposed system as an implantable drug delivery platform in the future.
A miniature controllable drug delivery device in which drug release is achieved by actuating polymeric valves is introduced. The valves made in flap configuration are bilayer structures which were fabricated as a thin gold film and an electrochemically deposited polypyrrole (PPy) layer. A drug simulate was stored in a reservoir and the drug release process was accomplished by bending the bilayer flaps with a small electrical potential bias in solution. The detailed fabrication procedures of this controllable drug delivery device are presented.
A controlled drug delivery system in which drug release is achieved by actuating an array of polymeric valves on a set of drug reservoirs is introduced. The valves are bilayer structures with one layer, a thin film of evaporated gold and the other, electrochemically deposited polypyrrole, which is also called “artificial muscle”. The valves are made in the shape of flaps fixed on one side to the valve seats. Drug reservoirs are covered by an array of such valves. Release of the drugs stored in the reservoirs is accomplished by bending the bilayer flaps back with a small applied bias. The fabrication procedures and proof-of-principle drug release experiments for this controlled drug delivery device are described. Energy consumption of this reversible valve design is compared with metal corrosion based valves developed earlier by other groups and our group.
A controlled drug delivery system in which drug release is achieved by actuating an array of polymeric valves on a set of drug reservoirs is introduced. The valves are bilayer structures, with one layer a thin film of evaporated gold and the other electrochemically deposited polypyrrole. The valves are made in the shape of flaps fixed on one side to the valve seats. Drug reservoirs are covered by an array of such valves, and release of the drugs stored in the reservoirs is accomplished by bending the bilayer flaps back with a small applied bias. The fabrication procedures and proof-of-principle drug release experiments for this controlled drug delivery device are described. Energy consumption of this reversible valve design is compared with metal corrosion based valves developed earlier by other and our group.