Permeability Barriers for Nicotine and Mannitol in Porcine Buccal Mucosa Studied by High-Resolution MALDI Mass Spectrometry Imaging

Marxen, Eva; Jacobsen, Jette Bredahl; Hyrup, Birgitte; Janfelt, Christian

doi:10.1021/acs.molpharmaceut.7b00891

Cited by 15 publications

(12 citation statements)

References 34 publications

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“…MALDI-MSI has been demonstrated to provide enough spatial resolution to be useful in providing qualitative drug distribution and penetration information on different types of tissues, 4,5,29,30 but it is not the ideal technique for quantification. From the present results, it thus cannot be inferred which of the three active drug substances is actually present at the highest concentration in the deeper layers.…”

Section: Discussionmentioning

confidence: 99%

Visualisation of penetration of topical antifungal drug substances through mycosis‐infected nails by matrix‐assisted laser desorption ionisation mass spectrometry imaging

Pinto

Bagger

Kunze

et al. 2020

Mycoses

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Background Matrix‐assisted laser desorption ionisation mass spectrometry imaging (MALDI‐MSI) is a mass spectrometry‐based technique, which can be applied for compound‐specific imaging of pharmaceuticals in tissues samples. MALDI‐MSI technology is widely used to visualise penetration and distribution profile through different tissues but has never been used with nail tissue. Objectives This study used MALDI‐MSI technology to visualise distribution profile and penetration into ex vivo human mycosis‐infected toenails of three antifungal active ingredients amorolfine, ciclopirox and naftifine contained in topical onychomycosis nail treatment preparations, marketed as Loceryl®, Ciclopoli® and Exoderil®. Methods Three mycosis‐infected toenails were used for each treatment condition. Six and twenty‐four hours after one single topical application of antifungal drugs, excess of formulation was removed, nails were cryo‐sectioned at a thickness of 20 μm, and MALDI matrix was deposited on each nail slice. Penetration and distribution profile of amorolfine, ciclopirox and naftifine in the nails were analysed by MALDI‐MSI. Results All antifungal actives have been visualised in the nail by MALDI‐MSI. Ciclopirox and naftifine molecules showed a highly localised distribution in the uppermost layer of the nail plate. In comparison, amorolfine diffuses through the nail plate to the deep layers already 6 hours after application and keeps diffusing towards the lowest nail layers within 24 hours. Conclusions This study shows for the first‐time distribution and penetration of certain antifungal actives into human nails using MALDI‐MSI analysis. The results showed a more homogeneous distribution of amorolfine to nail and a better penetration through the infected nails than ciclopirox and naftifine.

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Section: Discussionmentioning

confidence: 99%

Visualisation of penetration of topical antifungal drug substances through mycosis‐infected nails by matrix‐assisted laser desorption ionisation mass spectrometry imaging

Pinto

Bagger

Kunze

et al. 2020

Mycoses

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“…The intercellular lipid content is migrated to the apical cell surface to fuse with cell membrane and the lipid content is discharged into intercellular space to form a barrier of 200 µm superficial layer [11]. Marxen et al [16] reported that epithelium acts as a strong barrier for the permeation of nicotine and mannitol across the porcine buccal epithelium and buccal submucosa. Nicotine permeability at submucosa (P app,submucosa = 2.41 × 10 -5 ± 0.17 × 10 -5 cm/s; thickness = 635 ± 55 µm) was significantly higher than the epithelium (P app,epithelium = 1.20 × 10 -5 ± 0.24 × 10 -5 cm/s; thickness = 423 ± 46 µm), irrespective of the thickness.…”

Section: Oral Mucosamentioning

confidence: 99%

Mucoadhesive Delivery System: A Smart Way to Improve Bioavailability of Nutraceuticals

Subramanian

2021

Foods

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The conventional oral administration of many nutraceuticals exhibits poor oral bioavailability due to the harsh gastric conditions and first-pass metabolism. Oral mucosa has been recognized as a potential site for the delivery of therapeutic compounds. The mucoadhesive formulation can adhere to the mucosal membrane through various interaction mechanisms and enhance the retention and permeability of bioactive compounds. Absorption of bioactive compounds from the mucosa can improve bioavailability, as this route bypasses the hepatic first-pass metabolism and transit through the gastrointestinal tract. The mucosal administration is convenient, simple to access, and reported for increasing the bioactive concentration in plasma. Many mucoadhesive polymers, emulsifiers, thickeners used for the pharmaceutical formulation are accepted in the food sector. Introducing mucoadhesive formulations specific to the nutraceutical sector will be a game-changer as we are still looking for different ways to improve the bioavailability of many bioactive compounds. This article describes the overview of buccal mucosa, the concept of mucoadhesion and related theories, and different techniques of mucoadhesive formulations. Finally, the classification of mucoadhesive polymers and the mucoadhesive systems designed for the effective delivery of bioactive compounds are presented.

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“…For these methods, the solution is removed from the receptor chamber at pre-determined time points to measure the drug permeation over time using a UV spectrophotometer or HPLC. More recently, the localisation of permeants within the oral mucosa itself has been visualised down to a micrometre scale resolution using matrix-assisted laser desorption ionisation-mass spectrometry imaging (MALDI-MSI) on sectioned tissue [ 84 ].…”

Section: Electrospun Mucoadhesive Materialsmentioning

confidence: 99%

Mucoadhesive Electrospun Fibre-Based Technologies for Oral Medicine

et al. 2020

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Oral disease greatly affects quality of life, as the mouth is required for a wide range of activities including speech, food and liquid consumption. Treatment of oral disease is greatly limited by the dose forms that are currently available, which suffer from short contact times, poor site specificity, and sensitivity to mechanical stimulation. Mucoadhesive devices prepared using electrospinning offer the potential to address these challenges by allowing unidirectional site-specific drug delivery through intimate contact with the mucosa and with high surface areas to facilitate drug release. This review will discuss the range of electrospun mucoadhesive devices that have recently been reported to address oral inflammatory diseases, pain relief, and infections, as well as new treatments that are likely to be enabled by this technology in the future.

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Permeability Barriers for Nicotine and Mannitol in Porcine Buccal Mucosa Studied by High-Resolution MALDI Mass Spectrometry Imaging

Cited by 15 publications

References 34 publications

Visualisation of penetration of topical antifungal drug substances through mycosis‐infected nails by matrix‐assisted laser desorption ionisation mass spectrometry imaging

Visualisation of penetration of topical antifungal drug substances through mycosis‐infected nails by matrix‐assisted laser desorption ionisation mass spectrometry imaging

Mucoadhesive Delivery System: A Smart Way to Improve Bioavailability of Nutraceuticals

Mucoadhesive Electrospun Fibre-Based Technologies for Oral Medicine

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