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

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 diffu...

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Detalles Bibliográficos
Autores principales: Battaglia, Alex, Nguyen, Thanh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694425/
https://www.ncbi.nlm.nih.gov/pubmed/29058303
http://dx.doi.org/10.1007/s40268-017-0212-x
Descripción
Sumario: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.