Electrically controlled nicotine delivery through Carbon nanotube membranes via electrochemical oxidation and nanofluidically enhanced electroosmotic flow.

A promising tool for nicotine addiction treatment is a programmable nicotine delivery device coupled to smart phone-assisted behavioral therapies. Key metrics for such a device are delivery of adjustable nicotine doses tailored to individual needs, compact size and power efficiency. Reported here is a detailed optimization of carbon nanotube (CNT) membrane fabrication based on electrochemical oxidation, to improve its electrically driven performance for nicotine fluxes and switching ON (-1.5 V)-OFF (0 V) flux ratio. ON- state nicotine flux of ~ 6 µmoles/cm2/h at -1.5 V applied bias was achieved allowing ~ 6-folds decrease in the size of device (4 cm2) to attain flux equivalent to high dose nicotine gum (1.1 µmoles/cm2/h). Application of + 1.5 V bias in OFF state reduced diffusional background flux, giving an ON (-1.5 V)/OFF (+ 1.5 V) flux ratio of 68 that enabled device to deliver between the highest nicotine gum (1.1 µmoles/cm2/h) and lowest nicotine patch (0.08 µmoles/cm2/h) doses, as well as taper off nicotine doses for long term addiction treatment. The nicotine transport mechanism was studied as a function of pH and applied bias, using neutral tracer molecule, showing a mechanism of both electroosmosis and electrophoresis in the atomically smooth nanofluidic pores of CNTs. Optimal power consumption/flux efficiency of 111(µW/cm2)/µmoles/cm2/h was achieved allowing watch-battery lifetimes of 7-62 days for conventional treatment dosing regimens. Bluetooth-enabled, remotely controlled CNT membrane system has potential for treatments of nicotine, opioid and alcohol addictions that needs dose adjustment with precise temporal control.

A preclinical evaluation of a programmable CNT membrane device for transdermal nicotine delivery in hairless Guinea pigs.

Nicotine replacement therapy in the form of transdermal nicotine patches and nicotine gums combined with behavioral counseling still has a low smoking cessation rate of 25%. A promising approach to smoking cessation is to remotely program variable transdermal nicotine delivery rates, with inputs from counselor and patient through a smartphone counseling application. A switchable carbon nanotube (CNT) membrane device has been developed for transdermal nicotine delivery that can be programmed to deliver variable doses matching those of nicotine patches (7, 14 and 21 mg/24 h) and nicotine gums (2 mg /4 mg). The performance of switchable devices was evaluated in vitro on flow-cell geometry and in vivo on the skin of hairless guinea pig (HGP). In vitro, CNT membrane devices successfully switched between therapeutically useful nicotine fluxes of 1.3-1.8 µmoles/cm2/h (ON, -1.5 V) and 0.17-0.23 µmoles/cm2/h (OFF, 0 V), corresponded to the higher doses of gum and nicotine patch fluxes. In vivo, a microdialysis membrane probe was implanted in skin of HGP to directly detect nicotine fluxes through the skin barriers into dialysate with high temporal resolution. The CNT membrane device on HGP skin resulted in an ON/OFF nicotine flux ratio 6.4 ±â€¯2.5 as detected in microdialysis membrane probe in skin. Compared to commercial nicotine patches, the device in ON state was approximately 2-2.4 times the commercial nicotine patch dose as measured by dialysate nicotine fluxes. These results enable smartphone-controlled, battery operated transdermal delivery devices that can be coupled to remote counseling apps for personalized smoking cessation therapy.

Smoking Cessation Potential of Smartphone-Assisted Behavioral Therapy Coupled to Programmable Carbon Nanotube Membrane Nicotine Delivery Device.

Smoking tobacco continues to be a worldwide major cause of premature death. Although combined behavioral and pharmacotherapy interventions can increase the smoking cessation rate to nearly 25%, the combined approach is generally economically unattainable, and the low success rate leaves large populations at risk. Reviewed are treatments following primarily the principles of cognitive behavioral therapy (CBT) and nicotine replacement therapy (NRT), based on an addiction disease model with reduced dopamine receptors. Particular emphasis is placed on technology-assisted (Internet and smartphone applications) behavioral therapy to reduce economic costs. For smartphone apps, the established clinical strategies of the "5 A's of intervention" and the "5 R's of motivation" should be used. Counseling generally identifies self-expansion behaviors to stimulate dopamine cascades in reward pathways, but success rates are generally low because these patients have fewer dopamine receptors. Timing pharmacological therapy to induce dopamine cascades during self-expansion therapy offers an important increase in CBT success rates. An ideal platform would be a smartphone app, using best CBT practices along with a carbon nanotube-based programmable nicotine delivery device. These devices release variable doses of nicotine to provide relief from sustained withdrawal symptoms and relapse events, and reinforcement of self-expansion behaviors.

Programmable carbon nanotube membrane-based transdermal nicotine delivery with microdialysis validation assay.

To evaluate the performance of switchable carbon nanotubes (CNT) membrane devices for transdermal nicotine delivery, we have developed an in-vitro microdialysis method that allow us to detect variable transdermal fluxes of nicotine through CNT devices and can be applied directly to in-vivo studies. Microdialysis membranes were placed beneath the porcine skin and its nicotine levels increased 6-8 times when the CNT membrane on skin was turned from OFF to ON state by application of bias. Fluxes in the ON state were approximately 3 times that of commercial nicotine patches and switching times were less than two hours, thus suggesting the improved therapeutic potential of our device. Blue tooth enabled CNT devices that can be programmed by smartphone and coupled with remote counseling application for enhanced smoking cessation treatments.