TY - JOUR

T1 - Visualization of the penetration modifying mechanism of laurocapram by Mass Spectrometry Imaging in buccal drug delivery

AU - Handler, Anne Mette

AU - Marxen, Eva

AU - Jacobsen, Jette

AU - Janfelt, Christian

N1 - Copyright © 2018 Elsevier B.V. All rights reserved.

PY - 2019/1/15

Y1 - 2019/1/15

N2 - The aim of the study was to visualize the penetration modifying effect of laurocapram on the delivery of diazepam and codeine across buccal mucosa by MALDI Mass Spectrometry Imaging (MALDI-MSI). A qualitative ex vivo study was carried out by mounting porcine buccal mucosa in Ussing chamber sliders and applying a pre-treatment of phosphate buffered saline (PBS) or a 50% (v/v) laurocapram:ethanol solution apically before incubation for 1 or 3 h with a 0.1 M diazepam or 0.1 M codeine solution. MALDI-MSI analysis was performed on vertical cryo-sections of porcine buccal mucosa. The analysis provided detailed images of the localisation of the drugs, laurocapram and endogenous lipids in the epithelium and connective tissue. While diazepam in the absence of laurocapram was distributed with a steady concentration gradient through the connective tissue, indicating passive diffusion, pre-treatment with laurocapram fundamentally altered the penetration of diazepam through the buccal mucosa. In the presence of laurocapram, the distribution of diazepam was restricted to areas where laurocapram itself was present, in particular in the outer epithelial cell layers and in certain islands in the connective tissue. In contrast, the penetration of codeine was unaffected by the presence of laurocapram in similar experiments. The co-localization of laurocapram and diazepam indicates a reservoir effect, which has previously been found in diffusion experiments in Ussing chambers. The major difference in the penetration of codeine and diazepam through the buccal mucosa in presence of laurocapram was explained by the physicochemical properties of the drugs. Codeine is characterized by being more hydrophilic than diazepam and was partly charged under the given experimental conditions.

AB - The aim of the study was to visualize the penetration modifying effect of laurocapram on the delivery of diazepam and codeine across buccal mucosa by MALDI Mass Spectrometry Imaging (MALDI-MSI). A qualitative ex vivo study was carried out by mounting porcine buccal mucosa in Ussing chamber sliders and applying a pre-treatment of phosphate buffered saline (PBS) or a 50% (v/v) laurocapram:ethanol solution apically before incubation for 1 or 3 h with a 0.1 M diazepam or 0.1 M codeine solution. MALDI-MSI analysis was performed on vertical cryo-sections of porcine buccal mucosa. The analysis provided detailed images of the localisation of the drugs, laurocapram and endogenous lipids in the epithelium and connective tissue. While diazepam in the absence of laurocapram was distributed with a steady concentration gradient through the connective tissue, indicating passive diffusion, pre-treatment with laurocapram fundamentally altered the penetration of diazepam through the buccal mucosa. In the presence of laurocapram, the distribution of diazepam was restricted to areas where laurocapram itself was present, in particular in the outer epithelial cell layers and in certain islands in the connective tissue. In contrast, the penetration of codeine was unaffected by the presence of laurocapram in similar experiments. The co-localization of laurocapram and diazepam indicates a reservoir effect, which has previously been found in diffusion experiments in Ussing chambers. The major difference in the penetration of codeine and diazepam through the buccal mucosa in presence of laurocapram was explained by the physicochemical properties of the drugs. Codeine is characterized by being more hydrophilic than diazepam and was partly charged under the given experimental conditions.

KW - Administration, Buccal

KW - Animals

KW - Azepines/administration & dosage

KW - Codeine/administration & dosage

KW - Diagnostic Imaging

KW - Diazepam/administration & dosage

KW - Mass Spectrometry

KW - Mouth Mucosa/metabolism

KW - Permeability/drug effects

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

KW - Swine

U2 - 10.1016/j.ejps.2018.11.011

DO - 10.1016/j.ejps.2018.11.011

M3 - Journal article

C2 - 30439495

VL - 127

SP - 276

EP - 281

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

ER -