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 -