Cellular Uptake of Coumarin-6 under Microfluidic Conditions into HCE-T Cells from Nanoscale Formulations

Pretor, Sascha; Bartels, Joana; Lorenz, Thomas; Dahl, Kenneth; Finke, Jan Henrik; Peterat, Gena; Krull, Rainer; Al-Halhouli, Ala’aldeen; Dietzel, Andreas; Büttgenbach, S.; Behrends, Sönke; Reichl, Stephan; Müller‐Goymann, Christel C.

doi:10.1021/mp500401t

Cited by 42 publications

(20 citation statements)

References 51 publications

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“…To determine the role of shear stress in wound healing, the effect of physiological shear stress on cell phenotype, such as cytoskeletal reorganization, must first be taken into consideration; exposing cells to shear following damage does not mimic the physiological environment where corneal epithelial cells have been exposed to blinking consistently and thus have adopted a phenotype associated with exposure to shear stress. It is also important to note that the current in vitro models used to assess corneal epithelial cell response to shear stress in previous work [25–27,43] and even our own are limited as they have not been designed to mimic the physiological ocular environment. New in vitro models will need to be developed to better characterize the corneal epithelial cell response to shear stress.…”

Section: Resultsmentioning

confidence: 99%

Corneal epithelial cells exposed to shear stress show altered cytoskeleton and migratory behaviour

et al. 2017

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Cells that form the corneal epithelium, the outermost layer of the cornea, are exposed to shear stress through blinking during waking hours. In this in vitro study, the effect of fluid shear stress on human corneal epithelial cells (HCECs) was investigated. Following exposure to shear stresses of 4 and 8 dyn/cm2, HCECs showed cytoskeletal rearrangement with more prominent, organized and elongated filamentous actin. Cytoskeletal changes were time-dependent, and were most significant after 24 hours of shear stress. Higher rates of migration and proliferation, as evaluated by a scratch assay, were also observed following 24 hours of low shear stress exposure (4 dyn/cm2). This result contrasted the poor migration observed in samples scratched before shear exposure, indicating that shear-induced cytoskeletal changes played a key role in improved wound healing and must therefore precede any damage to the cell layer. HCEC cytoskeletal changes were accompanied by an upregulation in integrin β1 and downregulation of ICAM-1. These results demonstrate that HCECs respond favourably to flow-induced shear stress, impacting their proliferation and migration properties as well as phenotype.

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Section: Resultsmentioning

confidence: 99%

Corneal epithelial cells exposed to shear stress show altered cytoskeleton and migratory behaviour

et al. 2017

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“…Despite the different fluorescence intensities of the formulations under study, in comparison to untreated cells, significantly higher integrated mean fluorescence intensity (iMFI) values were measured in both the cell lines, indicating a fast internalization of lipid droplets and loaded drugs. 6-Coumarin was chosen as fluorescent probe for the IL lipid matrix [19,20]. Instead, internalization of RAP and BVZ loaded in IL was investigated, after fluorescent labelling, because of their different physico-chemical properties.…”

Section: Biopharmaceutical Characterization Of Il MIXmentioning

confidence: 99%

Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment

Dianzani

Monge

Miglio

et al. 2020

Cancers

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Aims: Advanced melanoma is characterized by poor outcome. Despite the number of treatments having been increased over the last decade, current pharmacological strategies are only partially effective. Therefore, the improvement of the current systemic therapy is worthy of investigation. Methods: a nanotechnology-based poly-chemotherapy was tested at preclinical level. Temozolomide, rapamycin, and bevacizumab were co-loaded as injectable nanoemulsions for total parenteral nutrition (Intralipid®), due to suitable devices, and preliminarily tested in vitro on human and mouse cell models and in vivo on the B16-F10 melanoma mouse model. Results: Drug combination was efficiently loaded in the liquid lipid matrix of Intralipid®, including bevacizumab monoclonal antibody, leading to a fast internalization in tumour cells. An increased cytotoxicity towards melanoma cells, as well as an improved inhibition of tumour relapse, migration, and angiogenesis were demonstrated in cell models for the Intralipid®-loaded drug combinations. In preliminary in vivo studies, the proposed approach was able to reduce tumour growth significantly, compared to controls. A relevant efficacy towards tumour angiogenesis and mitotic index was determined and immune response was involved. Conclusions: In these preliminary studies, Intralipid® proved to be a safe and versatile poly-chemotherapy delivery system for advanced melanoma treatment, by acting on multiple mechanisms.

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“…Both DiI and Cou6 exhibit affinity to plasma membranes and other lipid structures [ 66 , 67 ], which is in line with their lipophilicity. Thus, rapid redistribution of coumarin 6 from nanocarriers into cell membranes was observed in the in vitro experiments [ 58 , 68 ]. The rate of coumarin 6 redistribution also depended on the type of the carrier and was higher in the case of the liposomes as compared to the solid lipid nanoparticles.…”

Section: Resultsmentioning

confidence: 99%

Fluorescently Labeled PLGA Nanoparticles for Visualization In Vitro and In Vivo: The Importance of Dye Properties

et al. 2021

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Fluorescently labeled nanoparticles are widely used for evaluating their distribution in the biological environment. However, dye leakage can lead to misinterpretations of the nanoparticles’ biodistribution. To better understand the interactions of dyes and nanoparticles and their biological environment, we explored PLGA nanoparticles labeled with four widely used dyes encapsulated (coumarin 6, rhodamine 123, DiI) or bound covalently to the polymer (Cy5.5.). The DiI label was stable in both aqueous and lipophilic environments, whereas the quick release of coumarin 6 was observed in model media containing albumin (42%) or liposomes (62%), which could be explained by the different affinity of these dyes to the polymer and lipophilic structures and which we also confirmed by computational modeling (log PDPPC/PLGA: DiI—2.3, Cou6—0.7). The importance of these factors was demonstrated by in vivo neuroimaging (ICON) of the rat retina using double-labeled Cy5.5/Cou6-nanoparticles: encapsulated Cou6 quickly leaked into the tissue, whereas the stably bound Cy.5.5 label remained associated with the vessels. This observation is a good example of the possible misinterpretation of imaging results because the coumarin 6 distribution creates the impression that nanoparticles effectively crossed the blood–retina barrier, whereas in fact no signal from the core material was found beyond the blood vessels.

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Cellular Uptake of Coumarin-6 under Microfluidic Conditions into HCE-T Cells from Nanoscale Formulations

Cited by 42 publications

References 51 publications

Corneal epithelial cells exposed to shear stress show altered cytoskeleton and migratory behaviour

Corneal epithelial cells exposed to shear stress show altered cytoskeleton and migratory behaviour

Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment

Fluorescently Labeled PLGA Nanoparticles for Visualization In Vitro and In Vivo: The Importance of Dye Properties

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