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

https://doi.org/10.1016/j.nano.2016.06.017Get rights and content

Abstract

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.

Graphical abstract

Carbon nanotube (CNT) membranes have the ability to be switched by small applied bias and can improve smoking cessation therapy by the transdermal delivery of a variable nicotine flux/dose as set by remote therapy. However, a new transdermal assay need to be developed to show switching events of such devices. A microdialysis membrane probe was placed beneath porcine skin on the flow cell apparatus to capture nicotine molecules for flux analysis showing 6–8 times increase in nicotine level with device in on state and 3 times that of commercially available Nicoderm. This study for the first time demonstrates the feasibility of a microdialysis method for demonstrating switchable transdermal drug delivery devices.

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Section snippets

Fabrication and characterization of double-walled carbon nanotubes (DWCNT) membranes

DWCNT with average inner diameter of 1.3-2 nm and length of 50 μm were purchased from Sigma-Aldrich Corporation (St. Louis, MO, USA). A JEOL 2010F Transmission Electron Microscope (TEM) was used to see the diameter of as-purchased DWCNT. DWCNT membranes were fabricated as reported previously.19, 26 Briefly after a sonication/dispersion step, 2.5 wt% DWCNTs were mixed into Epon 862 epoxy resin (Miller-Stephenson Chemical Co., IL, USA), hardener methyl hexahydrophthalic anhydride (MHHPA,

CNT membrane fabrication and characterization

Double walled carbon nanotubes (DWCNT) membranes were fabricated using microtome cutting method as previously reported.19 SEM cross-section view of CNT membranes (Figure 2, A) showed that the membrane formed by microtoming a nanotube-epoxy composite mixture was 5 μm thick and the spaces between CNT were completely filled with the epoxy resin. Bundles of nanotubes were not observed, indicating the uniform dispersion of nanotubes in epoxy. TEM image of as-purchased DWCNTs showed pristine

Discussion

The key merit of CNT membranes as a delivery platform is the energy efficient pumping through atomically smooth graphitic cores allowing for high ON/OFF ratios with watch batteries lasting up to 10 days pumping potent therapeutics such as nicotine.19 With anionic dye functionalization at CNT pore entrances, ~4 times greater rectification factor for ionic current was observed in the case of DWCNT-dye functionalized membranes as compared to as-made membranes suggested efficient gate keeper

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    SEM and TEM facilities support was provided by the Centre for Nanoscale Science and Engineering and Electron Microscopy Centre at the University of Kentucky, Lexington, KY. Financial support was provided by National Institutes of Health NIDA (R01DA018822).

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