Evaluation of fluorescence anisotropy to assess drug–lipid membrane partitioning

Pallicer, Juan M.; Krämer, Stefanie-Dorothea

doi:10.1016/j.jpba.2012.08.009

Cited by 18 publications

(11 citation statements)

References 42 publications

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“… a Ref . b Predicted using p K a GALAS tool of ACD/Laboratories 2015 release (Build 2726). c Ref . d PhysProp database accessed via EPISuite version 4.1. e Ref . f Ref . g Ref . h Ref . i Ref . j Ref . k Ref . l Ref . m Predicted using the UFZ-LSER database n Data of this study (see SI section S2 for more details). …”

Section: Methodsmentioning

confidence: 99%

Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays

Huchthausen

Mühlenbrink

König

et al. 2020

Chem. Res. Toxicol.

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Exposure assessment in in vitro cell-based bioassays is challenging for ionizable organic chemicals (IOCs), because they are present as more than one chemical species in the bioassay medium. Furthermore, compared to neutral organic chemicals, their binding to medium proteins and lipids is driven by more complex molecular interactions. Total medium concentrations (C total,medium ) and/or freely dissolved medium concentrations (C free,medium ) were determined for one neutral chemical and 14 IOCs (acids, bases, multifunctional) at concentrations relevant for determination of cytotoxicity and effect. C free,medium was measured in two in vitro bioassays at the time of dosing and after 24 h of incubation using solid-phase microextraction. C free,medium was maximally 1.7 times lower than the nominal concentrations (C nom ) for the hydrophilic chemicals (caffeine and lamotrigine). For the organic acids (naproxen, ibuprofen, warfarin, and diclofenac), C free,medium was by a factor of 4 lower than C nom at high concentrations, but the ratio was much higher at low concentrations, indicating a nonlinear binding behavior. The experimental C free,medium was also compared with C free,medium predicted with a mass balance model accounting for binding to medium proteins and lipids. The mass balance model performed well for five of the test chemicals (within a factor of 10), but it underestimated C free,medium by up to a factor of 1200 for chemicals that showed nonlinear binding to medium components. These findings emphasize that experimental exposure assessment is required for improved understanding of in vitro toxicity data.

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Section: Methodsmentioning

confidence: 99%

Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays

Huchthausen

Mühlenbrink

König

et al. 2020

Chem. Res. Toxicol.

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“…The change in anisotropy has been used, for example, to investigate the interaction of different drug molecules with liposomes. 34 II.3. Time-Resolved Fluorescence.…”

Section: Methodsmentioning

confidence: 99%

Monitoring the Collapse of pH-Sensitive Liposomal Nanocarriers and Environmental pH Simultaneously: A Fluorescence-Based Approach

Draffehn

Kumke

2016

Mol. Pharmaceutics

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Nowadays, the encapsulation of therapeutic compounds in so-called carrier systems is a very smart method to achieve protection as well as an improvement of their temporal and spatial distribution. After the successful transport to the point of care, the delivery has to be released under controlled conditions. To monitor the triggered release from the carrier, we investigated different fluorescent probes regarding their response to the pH-induced collapse of pH-sensitive liposomes (pHSLip), which occurs when the environmental pH falls below a critical value. Depending on the probe, the fluorescence decay time as well as fluorescence anisotropy can be used equally as key parameters for monitoring the collapse. Especially the application of a fluorescein labeled fatty acid (fPA) enabled the monitoring of the pHSLips collapse and the pH of its microenvironment simultaneously without interference. Varying the pH in the range of 3 < pH < 9, anisotropy data revealed the critical pH value at which the collapse of the pHSLips occurs. Complementary methods, e.g., fluorescence correlation spectroscopy and dynamic light scattering, supported the analysis based on the decay time and anisotropy. Additional experiments with varying incubation times yielded information on the kinetics of the liposomal collapse.

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“…If the emission is highly polarized (approximately or equal to one), the molecules will not rotate between absorption and emission, which would suggest that they are associated with macromolecules. Therefore, the emission of polarization is described as anisotropy [48–49]. Furthermore, this measurement can be used to characterize specific or nonspecific linking as it is dependent on the fraction of fluorescent solute interacting with macromolecules or on the rigidity of the formed complex [48].…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the emission of polarization is described as anisotropy [48–49]. Furthermore, this measurement can be used to characterize specific or nonspecific linking as it is dependent on the fraction of fluorescent solute interacting with macromolecules or on the rigidity of the formed complex [48]. Anisotropy values close to zero are related to depolarized emission and intense molecule rotation [49].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Design of a nanostructured mucoadhesive system containing curcumin for buccal application: from physicochemical to biological aspects

Ferreira¹,

Braga²,

Oliveira³

et al. 2019

Beilstein J. Nanotechnol.

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Mucoadhesive nanostructured systems comprising poloxamer 407 and Carbopol 974P® have already demonstrated good mucoadhesion, as well as improved mechanical and rheological properties. Curcumin displays excellent biological activity, mainly in oral squamous cancer; however, its physicochemical characteristics hinder its application. Therefore, the aim of this study was to develop nanostructured formulations containing curcumin for oral cancer therapy. The photophysical interactions between curcumin and the formulations were elucidated by incorporation kinetics and location studies. They revealed that the drug was quickly incorporated and located in the hydrophobic portion of nanometer-sized polymeric micelles. Moreover, the systems displayed plastic behavior with rheopexy characteristics at 37 °C, viscoelastic properties and a gelation temperature of 36 °C, which ensures increased retention after application in the oral cavity. The mucoadhesion results confirmed the previous findings with the nanostructured systems showing a residence time of 20 min in porcine oral mucosa under flow system conditions. Curcumin was released after 8 h and could permeate through the porcine oral mucosa. Cytotoxicity testing revealed that the formulations were selective to cancer cells over healthy cells. Therefore, these systems could improve the physicochemical characteristics of curcumin by providing improved release and permeation, while selectivity targeting cancer cells.

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Evaluation of fluorescence anisotropy to assess drug–lipid membrane partitioning

Cited by 18 publications

References 42 publications

Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays

Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays

Monitoring the Collapse of pH-Sensitive Liposomal Nanocarriers and Environmental pH Simultaneously: A Fluorescence-Based Approach

Design of a nanostructured mucoadhesive system containing curcumin for buccal application: from physicochemical to biological aspects

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