Journal article
Electrospun α-lactalbumin nanofibers for site-specific and fast-onset delivery of nicotine in the oral cavity: an in vitro, ex vivo and tissue spatial distribution study
Nicotine replacement therapy (NRT) formulations for oromucosal administration induce a delayed rise in nicotine blood levels as opposed to the immediate nicotine increase obtained from cigarette smoking; this being a shortcoming of the therapy. Here, we demonstrate that α-lactalbumin/polyethylene oxide (ALA/PEO) electrospun nanofibers constitute an efficient oromucosal delivery system for fast-onset nicotine delivery of high relevance for acute dosing NRT applications.
In vitro, nicotine-loaded nanofibers showed fast disintegration in water, with a weight loss up to 40% within minutes, and a faster nicotine release (26.1±4.6% after 1 min of incubation) of the loaded nicotine compared to two relevant marketed NRT formulations with a comparable nicotine dose (i.e. 7.9±5.1% and 2.2±0.3% nicotine was released from a lozenge and a sublingual tablet, respectively).
Model-fitting of the release data indicated that the release mechanism of nicotine from the hydrophilic nanofibers was possibly governed by more than one type of release phenomena. Remarkably, ex vivo studies using porcine buccal mucosa demonstrated a more efficient permeation of the nicotine released from the nanofibers (flux of 1.06±0.22 nmol/(cm2×min)) compared to when dosing even a ten-fold concentrated nicotine solution (flux of 0.17±0.14 nmol/(cm2×min)).
Moreover, MALDI MS imaging of ex vivo porcine buccal mucosa exposed to nicotine-loaded nanofibers clearly revealed higher amounts of nicotine throughout the epithelium, as well as in the lamina propria and submucosa of the tissue. Our findings suggest that nicotine-loaded ALA/PEO nanofibers have potential as a mucosal, fast-releasing and biocompatible delivery system for nicotine, which can overcome the limitations of current marketed NRTs.
Language: | English |
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Publisher: | American Chemical Society |
Year: | 2020 |
Pages: | 4189-4200 |
ISSN: | 15438392 and 15438384 |
Types: | Journal article |
DOI: | 10.1021/acs.molpharmaceut.0c00642 |
ORCIDs: | Chronakis, Ioannis S. , 0000-0002-7285-9100 , 0000-0003-2855-0568 and 0000-0002-4626-3426 |
Administration, Buccal Animals Cell Line, Tumor Cell Survival Drug Compounding Drug Delivery Systems Drug Liberation Epithelial Cells Epithelium Humans Lactalbumin MALDI mass spectrometry imaging MALDI massspectrometry imaging Mouth Mouth Mucosa Nanofibers Nicotine Smoking Cessation Swine Tissue Distribution Tobacco Use Cessation Devices electrospun protein nanofibers electrospun proteinnanofibers ex vivo tissue permeation in vitro characterization nicotine nicotine replacement therapy nicotinereplacement therapy