Effect of Permeation Enhancers on the Buccal Permeability of Nicotine: Ex vivo Transport Studies Complemented by MALDI MS Imaging

TY - JOUR

T1 - Effect of Permeation Enhancers on the Buccal Permeability of Nicotine

T2 - Ex vivo Transport Studies Complemented by MALDI MS Imaging

AU - Marxen, Eva

AU - Jin, Liang

AU - Jacobsen, Jette

AU - Janfelt, Christian

AU - Hyrup, Birgitte

AU - Nicolazzo, Joseph A

PY - 2018/3/1

Y1 - 2018/3/1

N2 - PURPOSE: The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers.METHODS: The impact of sodium taurodeoxycholate (STDC), sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and Azone® on the permeability of [3H]-nicotine and [14C]-mannitol (a paracellular marker) across porcine buccal mucosa was studied ex vivo in modified Ussing chambers. The distribution of nicotine, mannitol and permeation enhancers was imaged using using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI).RESULTS: Despite STDC significantly increasing permeability of [14C]-mannitol, no enhancing effect was seen on [3H]-nicotine permeability with any of the permeation enhancers. Rather, SDS and DMSO retarded nicotine permeability, likely due to nicotine being retained in the donor compartment. The permeability results were complemented by the spatial distribution of nicotine and mannitol determined with MALDI MSI.CONCLUSIONS: The buccal permeability of nicotine was affected in an enhancer specific manner, suggesting that nicotine primarily diffuses via the transcellular pathway. MALDI MSI was shown to complement ex vivo permeability studies and to be a useful qualitative tool for visualizing drug and penetration enhancer distribution in buccal mucosa.

AB - PURPOSE: The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers.METHODS: The impact of sodium taurodeoxycholate (STDC), sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and Azone® on the permeability of [3H]-nicotine and [14C]-mannitol (a paracellular marker) across porcine buccal mucosa was studied ex vivo in modified Ussing chambers. The distribution of nicotine, mannitol and permeation enhancers was imaged using using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI).RESULTS: Despite STDC significantly increasing permeability of [14C]-mannitol, no enhancing effect was seen on [3H]-nicotine permeability with any of the permeation enhancers. Rather, SDS and DMSO retarded nicotine permeability, likely due to nicotine being retained in the donor compartment. The permeability results were complemented by the spatial distribution of nicotine and mannitol determined with MALDI MSI.CONCLUSIONS: The buccal permeability of nicotine was affected in an enhancer specific manner, suggesting that nicotine primarily diffuses via the transcellular pathway. MALDI MSI was shown to complement ex vivo permeability studies and to be a useful qualitative tool for visualizing drug and penetration enhancer distribution in buccal mucosa.

KW - Administration, Buccal

KW - Animals

KW - Cheek

KW - Drug Compounding/methods

KW - Excipients/chemistry

KW - Models, Animal

KW - Mouth Mucosa/drug effects

KW - Nicotine/administration & dosage

KW - Oral Mucosal Absorption/drug effects

KW - Permeability

KW - Smoking Cessation/methods

KW - Smoking Cessation Agents/administration & dosage

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

KW - Sus scrofa

U2 - 10.1007/s11095-017-2332-y

DO - 10.1007/s11095-017-2332-y

M3 - Journal article

C2 - 29468320

SN - 0724-8741

VL - 35

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 3

M1 - 70

ER -