TY - JOUR

T1 - Electrospun α-lactalbumin nanofibers for site-specific and fast-onset delivery of nicotine in the oral cavity

T2 - an in vitro, ex vivo and tissue spatial distribution study

AU - Kalouta, Kleopatra

AU - Stie, Mai Bay

AU - Janfelt, Christian

AU - Chronakis, Ioannis S

AU - Jacobsen, Jette

AU - Mørck Nielsen, Hanne

AU - Foderà, Vito

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1021/acs.molpharmaceut.0c00642

DO - 10.1021/acs.molpharmaceut.0c00642

M3 - Journal article

C2 - 32885978

VL - 17

SP - 4189

EP - 4200

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 11

ER -