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


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Abstract

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 ± 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.

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