Barrier characteristics of epithelial cultures modelling the airway and intestinal mucosa: A comparison

Vllasaliu, Driton; Fowler, Robyn; Garnett, Martin C.; Eaton, Mike; Stolnik, Snow

doi:10.1016/j.bbrc.2011.10.108

Cited by 33 publications

(23 citation statements)

References 28 publications

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“…Epithelial tight junctions can be transiently widened [10] and this could offer a temporary corridor for nanomedicine absorption via the paracellular space. However, this approach is probably not feasible for transepithelial delivery of nanocarriers larger than about 10 --20 nm, based on the findings that epithelial absorption exponentially decreases with increasing molecular weight of macromolecules following tight junction opening [118,131].…”

Section: Mucosal Deliverymentioning

confidence: 98%

“…However, mucosal surfaces present a barrier to the movement of nanoparticulates [118] due to the existence of a number of barriers, including mucus and the almost continuous 'sheet' of membranes of closely associated epithelial cells. Other barriers are also important.…”

Section: Mucosal Deliverymentioning

confidence: 99%

“…Mucus presents a considerable barrier to the movement of nanoparticles [118,127] and one of the key benefits of PEGylated nanosystems in mucosal drug delivery is a reported improvement of nanoparticle diffusion across mucus following PEGylation [127][128][129][130]. Enhancement in particle diffusion in mucus has been reported to be dependent on the molecular weight of PEG and the coating density [128,129], with coating of short-length PEG at high density providing a more efficient nanoparticle diffusion in mucus gel [128].…”

Section: Mucosal Deliverymentioning

confidence: 99%

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PEGylated nanomedicines: recent progress and remaining concerns

Vllasaliu

Fowler²,

Stolnik

2013

Expert Opinion on Drug Delivery

Self Cite

112

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The advent of nanomedicine providing therapeutic options of refined performance continues. Although PEGylation as a tool to improve the pharmacokinetics of nanomedicines is well established and is used clinically, other benefits of 'PEGnology', including enhancement of physicochemical properties and/or biocompatibility of actives and/or drug carriers, as well as mucosal delivery, have attracted less attention. While concerns regarding the clinical use of PEGylated nanomedicines remain, evidence suggests that at least some safety issues may be controlled by adequate designs of nanosystems.

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Section: Mucosal Deliverymentioning

confidence: 98%

Section: Mucosal Deliverymentioning

confidence: 99%

Section: Mucosal Deliverymentioning

confidence: 99%

See 1 more Smart Citation

PEGylated nanomedicines: recent progress and remaining concerns

Vllasaliu

Fowler²,

Stolnik

2013

Expert Opinion on Drug Delivery

Self Cite

112

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“…Barrier capacity and trans-compartment transport of particles vary considerably between different tissue types. 89 Limited transport across the epithelia is one of the prime obstacles for therapeutic agents and nanomedicines reaching the adequate biological compartment, 1 as barrier systems are unable to evaluate and differentiate drug delivery systems for translocation from foreign particles, and therefore restrict the entry of the drug carriers, rendering the system invaluable and reducing its efficacy.…”

Section: Current Advances In Trans-barrier Internalizationmentioning

confidence: 99%

Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures

Murugan¹,

Choonara²,

Kumar³

et al. 2015

IJN

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Cellular internalization and trans-barrier transport of nanoparticles can be manipulated on the basis of the physicochemical and mechanical characteristics of nanoparticles. Research has shown that these factors significantly influence the uptake of nanoparticles. Dictating these characteristics allows for the control of the rate and extent of cellular uptake, as well as delivering the drug-loaded nanosystem intra-cellularly, which is imperative for drugs that require a specific cellular level to exert their effects. Additionally, physicochemical characteristics of the nanoparticles should be optimal for the nanosystem to bypass the natural restricting phenomena of the body and act therapeutically at the targeted site. The factors at the focal point of emerging smart nanomedicines include nanoparticle size, surface charge, shape, hydrophobicity, surface chemistry, and even protein and ligand conjugates. Hence, this review discusses the mechanism of internalization of nanoparticles and ideal nanoparticle characteristics that allow them to evade the biological barriers in order to achieve optimal cellular uptake in different organ systems. Identifying these parameters assists with the progression of nanomedicine as an outstanding vector of pharmaceuticals.

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“…This strategy however may be limited to relatively small biomolecules (peptides or small proteins), whilst systemic delivery of larger biotherapeutics ( e.g. antibodies or PEGylated antibody fragments) through this approach is shown to be inefficient [4]. Furthermore, the longer-term implications of repeated opening of the tight junctions are currently unclear.…”

Section: Introductionmentioning

confidence: 99%

Uptake and transport of B 12 -conjugated nanoparticles in airway epithelium

Fowler

Vllasaliu

Falcone

et al. 2013

Journal of Controlled Release

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Non-invasive delivery of biotherapeutics, as an attractive alternative to injections, could potentially be achieved through the mucosal surfaces, utilizing nanoscale therapeutic carriers. However, nanoparticles do not readily cross the mucosal barriers, with the epithelium presenting a major barrier to their translocation. The transcytotic pathway of vitamin B12 has previously been shown to ‘ferry’ B12-decorated nanoparticles across intestinal epithelial (Caco-2) cells. However, such studies have not been reported for the airway epithelium. Furthermore, the presence in the airways of the cell machinery responsible for transepithelial trafficking of B12 is not widely reported. Using a combination of molecular biology and immunostaining techniques, our work demonstrates that the bronchial cell line, Calu-3, expresses the B12-intrinsic factor receptor, the transcobalamin II receptor and the transcobalamin II carrier protein. Importantly, the work showed that sub-200 nm model nanoparticles chemically conjugated to B12 were internalised and transported across the Calu-3 cell layers, with B12 conjugation not only enhancing cell uptake and transepithelial transport, but also influencing intracellular trafficking. Our work therefore demonstrates that the B12 endocytotic apparatus is not only present in this airway model, but also transports ligand-conjugated nanoparticles across polarised epithelial cells, indicating potential for B12-mediated delivery of nanoscale carriers of biotherapeutics across the airways.

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Barrier characteristics of epithelial cultures modelling the airway and intestinal mucosa: A comparison

Cited by 33 publications

References 28 publications

PEGylated nanomedicines: recent progress and remaining concerns

PEGylated nanomedicines: recent progress and remaining concerns

Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures

Uptake and transport of B 12 -conjugated nanoparticles in airway epithelium

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Barrier characteristics of epithelial cultures modelling the airway and intestinal mucosa: A comparison

Cited by 33 publications

References 28 publications

PEGylated nanomedicines: recent progress and remaining concerns

PEGylated nanomedicines: recent progress and remaining concerns

Parameters and characteristics governing cellular internalization and trans-barrier trafficking of&nbsp;nanostructures

Uptake and transport of B 12 -conjugated nanoparticles in airway epithelium

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Product

Resources

About

Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures