Evaluation of a physiological<i>in vitro</i>system to study the transport of nanoparticles through the buccal mucosa

Roblegg, Eva; Frőhlich, Eleonore; Meindl, Claudia; Teubl, Birgit Johanna; Zaversky, Michaela; Zimmer, Andreas

doi:10.3109/17435390.2011.580863

Cited by 92 publications

(41 citation statements)

References 33 publications

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“…The permeability of 25 nm, 50 nm, and 200 nm PP particles through porcine buccal mucosa was first determined using standardized diffusion cells. Prior to every experiment, the viability and integrity of the used tissue was evaluated 17…”

Section: Resultsmentioning

confidence: 99%

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In‐Vitro Permeability of Neutral Polystyrene Particles via Buccal Mucosa

Teubl

Meindl

Eitzlmayr

et al. 2012

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Drugs can be absorbed well in the oral cavity, which eliminates problems related to intestinal and hepatic first-pass metabolism. Although it is well-established that nanoparticles are small enough to penetrate/permeate epithelial barriers, there is no clear understanding of how they interact with the buccal mucosa. This work provides useful information regarding particle properties with regard to mucosal uptake and can be used for the rational design of nanocarriers. In the buccal mucosa, the uptake of neutral polystyrene nanoparticles (PP) is size-dependent. Compared to 25 and 50 nm particles, 200 nm PP particles penetrate into deeper regions of the mucosa. This is attributed to the structure of the buccal mucosa, i.e., mucus layer and microplicae. The particles permeate the mucus layer and deposit in ridge-like folds of superficial buccal cells. Thus, the effects of thermodynamic driving forces and/or interparticle electrostatic repulsion are enhanced and cellular uptake might be reduced for smaller particle sizes.

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Section: Resultsmentioning

confidence: 99%

“…Our recent studies demonstrated that negatively charged 20 nm and positively charged 200 nm particles permeated the mucus layer whereas negatively charged 200 nm particles were entrapped within the mucus and formed aggregates 17…”

Section: Introductionmentioning

confidence: 99%

In‐Vitro Permeability of Neutral Polystyrene Particles via Buccal Mucosa

Teubl

Meindl

Eitzlmayr

et al. 2012

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“…Oral porcine mucosa is similar to the human one in ultrastructure and therefore an accepted alternative due to the limited availability of human oral mucosa. 10 Both full-thickness mucosal tissues, masticatory and buccal mucosa (Figure 2A Analyses revealed that the CMS nanocarrier penetrated the masticatory and the buccal mucosa. In the masticatory mucosa, the penetration of most particles was slightly deeper compared to the buccal mucosa but seemed to be limited to the stratum corneum with a penetration depth of 10 μm.…”

Section: The Core-multishell Indocarbocyanine Nanocarrier Penetratementioning

confidence: 96%

Characterization of hyperbranched core‐multishell nanocarriers as an innovative drug delivery system for the application at the oral mucosa

Jäger

Obst

Lohan

et al. 2017

J of Periodontal Research

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Background and Objectives In the oral cavity, the mucosal tissues may develop a number of different pathological conditions, such as inflammatory diseases (gingivitis, periodontitis) and autoimmune disorders (eg, oral lichen planus) that require therapy. The application of topical drugs is one common therapeutic approach. However, their efficacy is limited. Dilution effects due to saliva hinder the adherence and the penetration of drug formulations. Therefore, the bioavailability of oral topical drugs is insufficient, and patients may suffer from disease over years, if not life‐long. Material and Methods In the present study, we characterized core‐multishell (CMS) nanocarriers for their potential use as drug delivery systems at oral mucosal tissues. For this purpose, we prepared porcine masticatory as well as buccal mucosa and performed Franz cell diffusion experiments. Penetration of fluorescently labeled CMS nanocarriers into the mucosal tissue was analyzed using confocal laser scanning microscopy. Upon exposure to CMS nanocarriers, the metabolic and proliferative activity of gingival epithelial cells was determined by MTT and sulforhodamine B assays, respectively. Results Here, we could show that the carriers penetrate into both mucosal tissues, while particles penetrate deeper into the masticatory mucosa. Electron paramagnetic resonance spectroscopy revealed that the 3‐carboxy‐2,2,5,5‐tetramethyl‐1‐pyrrolidinyloxy‐labeled glucocorticoid dexamethasone loaded on to the CMS nanocarriers was released from the carriers in both mucosal tissues but with a higher efficiency in the buccal mucosa. The release from the nanocarriers is in both cases superior compared to the release from a conventional cream, which is normally used for the treatment of inflammatory conditions in the oral cavity. The CMS nanocarriers exhibited neither cytotoxic nor proliferative effects in vitro. Conclusion These findings suggested that CMS nanocarriers might be an innovative approach for topical drug delivery in the treatment of oral inflammatory diseases.

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“…30 Consequently, tissues were sliced into 5 mm samples after extensively washing them (n = 12). Half of the samples were boiled in water for 1 hour to inactivate the enzymes (zero value).…”

Section: Cell Viabilitymentioning

confidence: 99%

Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

Gradauer

Vonach²,

Leitinger³

et al. 2012

IJN

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Aim: To develop mucoadhesive liposomes by anchoring the polymer chitosan-thioglycolic acid (chitosan-TGA) to the liposomal surface to target intestinal mucosal membranes. Methods: Liposomes consisting of phosphatidylcholine (POPC) and a maleimide-functionalized lipid were incubated with chitosan-TGA, leading to the formation of a thioether bond between free SH-groups of the polymer and maleimide groups of the liposome. Uncoated and newly generated thiomer-coated liposomes were characterized according to their size, zeta potential, and morphology using photon correlation spectroscopy and transmission electron microscopy. The release behavior of calcitonin and the fluorophore/quencher-couple ANTS/DPX (8-aminonaphthalene-1,3,6-trisulfonic acid/p-xylene-bis-pyridinium bromide) from coated and uncoated liposomes, was investigated over 24 hours in simulated gastric and intestinal fluids. To test the mucoadhesive properties of thiomer-coated and uncoated liposomes in-vitro, we used freshly excised porcine small intestine. Results: Liposomes showed a concentration-dependent increase in size -from approximately 167 nm for uncoated liposomes to 439 nm for the highest thiomer concentration used in this study. Likewise, their zeta potentials gradually increased from about -38 mV to +20 mV, clearly indicating an effective coupling of chitosan-TGA to the surface of liposomes. As a result of mucoadhesion tests, we found an almost two-fold increase in the mucoadhesion of coupled liposomes relative to uncoupled ones. With fluorescence microscopy, we saw a tight adherence of coated particles to the intestinal mucus. Conclusion: Taken together, our current results indicate that thiomer-coated liposomes possess a high potential to be used as an oral drug-delivery system.

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Evaluation of a physiologicalin vitrosystem to study the transport of nanoparticles through the buccal mucosa

Cited by 92 publications

References 33 publications

In‐Vitro Permeability of Neutral Polystyrene Particles via Buccal Mucosa

In‐Vitro Permeability of Neutral Polystyrene Particles via Buccal Mucosa

Characterization of hyperbranched core‐multishell nanocarriers as an innovative drug delivery system for the application at the oral mucosa

Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

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