Original ArticleProgrammable carbon nanotube membrane-based transdermal nicotine delivery with microdialysis validation assay
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.
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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2020, Biopolymer-Based Formulations: Biomedical and Food ApplicationsA preclinical evaluation of a programmable CNT membrane device for transdermal nicotine delivery in hairless Guinea pigs
2019, Journal of Controlled ReleaseCitation Excerpt :After crossing the skin barrier, a proportional amount of nicotine diffuses into the dialysate of the hollow microdialysis fiber, allowing quantification of the nicotine delivery rate as a function of time. Previously, an ex vivo study with microdialysis membrane probes placed beneath porcine skin successfully showed variable dialysate nicotine fluxes through CNT membranes placed on the skin [13]. The ON state flux of CNT membranes was ~3 times higher than that of commercial nicotine patches.
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2018, Advanced Drug Delivery ReviewsCitation Excerpt :Programmed drug release was demonstrated by controlling the on/off cycles of the NIR laser. Gulati, et al. also implemented a switchable nicotine patch which used a carbon nanotube (CNT) membrane as a switching layer [126]. The permeability of the CNT membrane was changed when DC bias (~ 600 mV) was applied.
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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).