The Preparation And Properties Of The Thermally Responsive And Automatic Drug Delivery System Based On Polypyrrole

Inherently conducting polymers(ICPs) such as polypyrrole(PPy) have proven to be suitable reservoirs for accommodating active species for controlled release due to their unique redox properties which involving the entry of anions during oxidation and expulsion during reduction.To date,there are generally two types of controlled release systems based on the ICPs.The first type supplies chemicals or drugs by applying a negative potential to reduce the ICPs,which offers the possibility of controllable drug administration through electrical stimulation but has limitation of requiring external power source.The second type is constructed based on the galvanic cell mechanism and the triggered release occurs by connecting the dopant incorporated ICPs electrode(cathode) to a metal counter electrode with low anodic potential(anode) in an electrolyte.This system requires no external power supply,and a range of biodegradable polymer coating on the metal anode used to control the rate of drug release.However,it is difficult to manage the release process on demand because the onset of release is dependent on the external connection of the ICPs cathode to the metal anode.It is obvious that the two separated electrodes also make the system inconvenient to operate and especially unsuitable for the application in such area as implantable drug delivery systems.In this paper,we develop a convenient method for the fabrication of a new drug delivery system based on the galvanic cell mechanism by simply electrodeposition of the drug incorporated PPy directly on the one surface of a titanium sheet.After electrodeposition of ATP-doped PPy(PPy/ATP) on one side of titanium sheet,an eicosane-poly(L-lactic acid) thin film was coated evenly on the opposite side to cover the naked titanium completely.A self-powered,thermally responsive,easy operated,and structure simple drug delivery system was fabricated and has a good application prospects in the field of drug delivery.The main work and results included as following: 1) PPy/ATP film was electrochemically polymerized at a constant current density on the one surface of a titanium sheet,a galvanic cell containing PPy/ATP cathode and titanium anode in PBS was fabricated after the opposite titanium was exposed.It was found that:large quantity of ATP was released under the control of electromotive force,and more active metals,more porous PPy film and higher temperature result in the increasing of ATP release rate.2) An eicosane-poly(L-lactic acid) thin film was coated on the exposed titanium,a thermally responsive and automatic drug delivery system based on PPy was fabricated.It was found that:ATP was released little at room temperature while large quantity at body temperature.3) ATP release mechanism was demonstrated by detecting the released titanium ions and the electromotive force.It was found that:Eicosane/PLLA thin film was insulator and able to isolate the titanium from the surrounding electrolytic solution.As a result,no current flowed in the system and thus ATP could not be released.However, because the melting point of eicosane was 36.8℃,as the temperature rose to the body temperature(～37.5℃),eicosane melted and the titanuim underneath was exposed, allowing the redox reaction to be initiated and accompanied with the release of ATP.4) A drug release model was constructed by theoretical calculations.It was found that:the release rate v had a direct propotion relationship with t^1/2 exp(- kt).5) The cytocompatibility of ATP release system was evaluated by MTT assay.It was found that the ATP release system had a good cytocompatibility.