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Published in: Drugs in R&D 4/2017

Open Access 01-12-2017 | Original Research Article

Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis

Authors: Alex Battaglia, Thanh Nguyen

Published in: Drugs in R&D | Issue 4/2017

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Abstract

Background and Objective

The aim of this study was to test the hypothesis that tincture of benzoin (TOB) facilitates immediate transmucosal nicotine absorption while simultaneously promoting a safe and sustained delivery of the nicotine.

Methods

In combination with TOB, nicotine toxicity and diffusion across human mucosal cells were measured using a 3-D human mucosal tissue model.

Results

Nicotine was delivered 2.1 times more quickly in combination with TOB than in combination with saline (p < 0.05). Despite the increased diffusion, nicotine in combination with TOB significantly increased mucosal cell survival (p < 0.05) by reducing the release of mitochondrial cytochrome c into the cytoplasm when compared with nicotine without TOB. The average percentage distribution of cytochrome c in the cytosolic fraction over time of nicotine + 79% ethyl alcohol (ETOH) versus nicotine plus TOB (79% ETOH) was significantly different over 120 min (60.0 ± 29.9% cytosol, 16.1 ± 9.4% cytosol, p = 0.03). Related to the reduction of cytochrome c release into the cytoplasm, TOB suppressed caspase-3 and -9 activity, thereby preventing intrinsic apoptosis and providing cytoprotection of the mucosal cells (ETOH + nicotine vs ETOH + nicotine + TOB: p = 0.008 for caspase 3, p < 0.001 for caspase 9).

Conclusion

Two hours of TOB (17–24% benzoin, 79% ETOH) plus nicotine promotes diffusion of nicotine across human mucosal cells and simultaneously prevents human mucosal cell toxicity by inhibiting cytochrome c release into the cytosol, thereby preventing caspase 3 and 9 activity and subsequent intrinsic apoptosis.
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Metadata
Title
Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis
Authors
Alex Battaglia
Thanh Nguyen
Publication date
01-12-2017
Publisher
Springer International Publishing
Published in
Drugs in R&D / Issue 4/2017
Print ISSN: 1174-5886
Electronic ISSN: 1179-6901
DOI
https://doi.org/10.1007/s40268-017-0212-x

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