Methods to determine the interactions of micro- and nanoparticles with mucus

Grießinger, Julia Anita; Dünnhaupt, Sarah; Cattoz, Beatrice; Griffiths, Peter Charles; Oh, Sejin; Borrós, Salvador; Wilcox, Matthew; Pearson, Jeffrey P.; Gumbleton, Mark; Abdulkarim, Muthanna; Sousa, Irene Pereira de; Bernkop‐Schnürch, Andreas

doi:10.1016/j.ejpb.2015.01.005

Cited by 103 publications

(74 citation statements)

References 81 publications

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“…This method shows great promise for the future. There has been a significant amount of research on the use of particles as delivery systems through mucus and as a consequence a wide range of methods have been used many of which have been described an a recent review by Griessinger et al The quartz crystal microbalance with dissipation (QCM‐D) has been used to assess the combined properties between mucoadhesion and permeability of thiolated chitosans and their complexes with a layer of native porcine gastric mucin …”

Section: Methods For Characterizing Mucus Permeabilitymentioning

confidence: 99%

Innovative Methods and Applications in Mucoadhesion Research

Mackie

Goycoolea

Menchicchi

et al. 2017

Macromolecular Bioscience

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The present review is aimed at elucidating relatively new aspects of mucoadhesion/mucus interaction and related phenomena that emerged from a Mucoadhesion workshop held in Munster on 2-3 September 2015 as a satellite event of the ICCC 13th-EUCHIS 12th. After a brief outline of the new issues, the focus is on mucus description, purification, and mucus/mucin characterization, all steps that are pivotal to the understanding of mucus related phenomena and the choice of the correct mucosal model for in vitro and ex vivo experiments, alternative bio/mucomimetic materials are also presented. Then a selection of preparative techniques and testing methods are described (at molecular as well as micro and macroscale) that may support the pharmaceutical development of mucus interactive systems and assist formulators in the scale-up and industrialization steps. Recent applications of mucoadhesive systems (including medical devices) intended for different routes of administration (oral, gastrointestinal, vaginal, nasal, ocular, and intravesical) and for the treatment of difficult to treat pathologies or the alleviation of symptoms are described.

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Section: Methods For Characterizing Mucus Permeabilitymentioning

confidence: 99%

Innovative Methods and Applications in Mucoadhesion Research

Mackie

Goycoolea

Menchicchi

et al. 2017

Macromolecular Bioscience

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“…pylori . 12,48,49,50 On the other hand, several studies considering macromolecules/particles diffusion in mucus use mimic models based on commercial mucins or mixtures thereof, 51,52,53,54 which are still far from the real native gastric mucus. By PAGE, we could confirm the integrity of both oligonucleotides in native gastric mucus.…”

Section: Discussionmentioning

confidence: 99%

Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori

Santos

Dakwar

Xiong

et al. 2015

Molecular Therapy - Nucleic Acids

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Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid mimics are a promising alternative. In particular, locked nucleic acids (LNA)/2'-OMethyl RNA (2'OMe) have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical barriers—the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without permeabilization and fixation of the bacteria, which is normally part of in vitro studies, the ability of LNA/2'OMe to efficiently hybridize with H. pylori was hampered by the presence of mucus. Future research should focus on developing nanocarriers that shield LNA/2'OMe from components in the gastric mucus, while remaining capable of diffusing through the mucus and delivering these nucleic acid mimics directly into the bacteria.

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“…Consequently the mucin has been denatured and its ability to form mucin:mucin interactions is lost, which results in its inability to form a gel [83,84]. This commercial preparation has even been used to study mucin phase behavior, which must be affected by the quality of the mucin preparation [85].…”

Section: Mucus Models For Permeation/transport Studiesmentioning

confidence: 98%

The Properties of the Mucus Barrier, a Unique Gel–How Can Nanoparticles Cross It?

2016

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The key criterion for a nanoparticle drug-delivery system is the ability to produce substantial bioavailability without damaging the physiological protective mechanisms. The main area for drug delivery is the aerodigestive tract. All epithelial surfaces have a membrane-bound layer and in the lung this layer is surmounted by a gel layer. In the gastrointestinal tract the membrane-bound mucin layer is covered by a mucus bilayer. The pore sizes of mucus gels are around 100 to 200 nm. Consequently, only nanoparticles in this size range could potentially penetrate without modification of these layers. To study nanoparticle permeation with results that pertain to in vivo conditions, native mucus mucin preparations must be used. Strategies to increase pores in mucus gels are discussed herein.

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Methods to determine the interactions of micro- and nanoparticles with mucus

Cited by 103 publications

References 81 publications

Innovative Methods and Applications in Mucoadhesion Research

Innovative Methods and Applications in Mucoadhesion Research

Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori

The Properties of the Mucus Barrier, a Unique Gel–How Can Nanoparticles Cross It?

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