PEDOT Membranes as Electrically Tuneable Barriers for Nicotine Delivery

Abstract

Introduction: Tobacco smoking is a major public health concern and is the number one cause of disease and preventable death worldwide. Nicotine replacement therapy is widely available to promote smoking cessation; however, these treatments do not achieve the high levels of nicotine in the body required to satisfy acute cravings. There is a requirement to develop new drug delivery systems with the ability to titrate doses of nicotine during acute cravings. Poly(3,4-ethylenedioxythiophene) (PEDOT) is an electroactive polymer with properties that can be modified using electrical stimuli which can be used as membranes for on-demand drug release. We hypothesise that changes in the flux of nicotine (MW-162.2 Da) through PEDOT membranes can be achieved upon electrical stimulation. In the future these membranes could form a central component of an implantable delivery system for on-demand release of nicotine. To further explore the ability of PEDOT to act as electrically tuneable rate controlling membrane, we also investigated the flux of different drug molecules with larger size, dexamethasone phosphate (MW-516.4 Da) and lactoferrin (MW-80 kDa). Aims: To prepare free standing, mechanically robust and reversibly electroactive PEDOT membranes by vacuum vapour phase polymerisation. To explore the potential of these PEDOT membranes to act as electrically tuneable barriers to nicotine flux. In addition to nicotine, the flux of larger molecules such as dexamethasone phosphate and lactoferrin through PEDOT membranes with and without electrical stimulation was also explored. Methods: Variations in vacuum vapour phase polymerisation conditions were investigated and optimised to obtain free standing, mechanically robust and electroactive PEDOT membranes. These membranes were characterised by cyclic voltammetry to determine reversible electroactivity, optical profilometry to measure thickness, four-point probe conductivity meter to measure conductivity, texture analyser to determine mechanical robustness, scanning electron microscopy for surface morphology and infrared spectroscopy to investigate intermolecular interactions. The flux of three different drugs through PEDOT membranes was investigated with and without electrical stimulation using a customised Franz cell setup with 3D printed donor compartments. Results and Discussion: PEDOT membranes were successfully prepared which were suitable to act as free-standing rate controlling membranes with a thickness of 1.66 ± 0.06 μm, high conductivity of 1550 ± 60 S/cm, reversible electroactivity and mechanical strength of 29.35 ± 3.25 N/mm2. Scanning electron microscopy of the PEDOT membranes demonstrated a smooth and uniform surface. The flux of nicotine through PEDOT membranes could not be controlled by electrical stimulation (two tailed t-tes,t p>0.05) which can be attributed to the small size and permeable nature of nicotine. Meanwhile, lactoferrin, the largest molecule tested was unable to pass through the PEDOT membrane. However, the flux of dexamethasone phosphate could be electrically controlled through PEDOT membranes, the highest rate of flux (6.64 ± 2.94 mg/cm2/h) was achieved when PEDOT was maintained in the oxidised state in comparison to no electrical stimulation (4.42 ± 0.84 mg/cm2/h) (p< 0.05). Conclusion: Vacuum vapour phase polymerisation is an appropriate route to prepare mechanically robust and electroactive PEDOT membranes. While the flux of nicotine could not be controlled through the PEDOT membranes, due to small size and high permeability, these membranes did function as electrically tuneable barriers to dexamethasone phosphate flux. In the future PEDOT membranes such as these could form a central component of implantable delivery systems for on-demand release of drugs of appropriate size where dosing can be controlled by electrical stimuli.