Relationships between human intestinal absorption and polar interactions drug/phospholipids estimated by IAM–HPLC.

Grumetto, Lucia; Russo, Giacomo; Barbato, Francesco

doi:10.1016/j.ijpharm.2015.04.062

Cited by 29 publications

(25 citation statements)

References 39 publications

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“…The regression model’s obtained results showed that even though there was a suitable fitting between the iLOGP and log k ’ IAM variables (both physicochemical parameters carry similar information regarding lipophilicity), they do not encode the same information regarding specific interactions, as shown below. This fact agrees with the other reports ( Grumetto et al, 2015a ; Russo et al, 2017 ) which proposed that when a compound is ionizable and/or presents a polar surface area ≠ 0, the interactions with the two partition phases, i.e., n-octanol and phospholipids, are differently affected by electrostatic and polar interaction forces. Thus, it may be concluded that the balance between polar and hydrophobic effects is not the same toward the n-octanol and IAM phases.…”

Section: Discussionsupporting

confidence: 93%

“…To estimate cellular permeability there have been several absorption models that are proposed, including cell-based models, using the human colorectal adenocarcinoma (Caco-2) cell line and the Madin-Darby Canine Kidney (MDCK) cell line and tissue-based models, such as in situ rat intestinal perfusion or the Ussing chamber system employing rat or human intestinal tissues ( Berben et al, 2018 ). Although these models are useful in terms of permeability prediction, they have several drawbacks, including high-cost and complex experimental procedures as well as ethical issues associated with animal-based assays ( Grumetto et al, 2015a ).…”

Section: Introductionmentioning

confidence: 99%

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Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers

et al. 2021

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Among healthy vegetables, those of the genus Allium stand out. Antioxidant and anti-inflammatory properties have been associated with these vegetables, attributed mainly to organosulfur compounds (OSCs). In turn, they are linked to a protective effect counteracting cardiovascular disease development. Now, to really ensure the bioactive efficacy of the said compounds once consumed, it is necessary to previously evaluate the ADME (absorption, distribution, metabolism, and excretion) profile. Alternatively, in vitro and in silico methods attempt to avoid or reduce experimental animals’ use and provide preliminary information on drugs’ ability to overcome the various biological barriers inherent in the ADME process. In this sense, in silico methods serve to provide primary information on drugs’ bioavailability mechanisms. High-performance liquid chromatography (HPLC) using a stationary phase composed of phospholipids, the so-called immobilized artificial membrane (IAM), has been widely recognized as a valuable alternative method to extract and quantify information about the structure and physicochemical properties of organic compounds which are extensively used in studies of quantitative structure–activity relationships (QSARs). In the present study, the chromatographic capacity factors (log k’ (IAM)) for 28 OSCs were determined by IAM-HPLC. In order to evaluate the ability of the IAM phase in assessing lipophilicity of the compounds under study, several quantitative structure–retention relationships (QSRRs) were derived from exploring fundamental intermolecular interactions that govern the retention of compounds under study on IAM phases. As expected, the hydrophobic factors are of prime importance for the IAM retention of these compounds. However, the molecular flexibility and specific polar interactions expressed by several electronic descriptors (relative negative charge, RNCG, and Mulliken electronegativity) are also involved. We also evaluated the IAM phase ability to assess several ADME parameters for the OSCs under study obtained using the SwissADME web tool integrated into the SwissDrugDesign workspace and the PreADMET web tool. The human gastrointestinal absorption (HIA), blood–brain barrier (BBB) permeation, and skin permeability were investigated through QSAR modeling, using several chemometric approaches. The ADME properties under study are strongly dependent on hydrophobic factors as expressed by log k’(IAM), which provide evidence for the great potential of the IAM phases in the development of QSAR models.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers

et al. 2021

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“…their affinity for phospholipids. Such measures have been proven to be able to mirror various phenomena underlying membrane barrier passage 8,[11][12][13] . In addition, other chromatographic indexes, whose drug BBB-penetration predictivity has been demonstrated 14-16 , include those achieved by Micellar Liquid Chromatography (MLC) technique.…”

Section: Introductionmentioning

confidence: 99%

“…Conversely, the static properties are much faster to calculate. Performing the weighted average of the conformational properties yielded the most predictive models (equations(11) and(12)) and in those relationships, verapamil again behaved as an outlier, suggesting that such models would not be able to mirror the penetration of analytes undergoing some sort of active transport, in this case P-gp mediated efflux. It is interesting to point out how, among the ionized properties employed for the statistical method development (equations (9) and (10)), no one depends noticeably on ionization.…”

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confidence: 99%

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Determination of in Vitro and in Silico Indexes for the Modeling of Blood–Brain Barrier Partitioning of Drugs via Micellar and Immobilized Artificial Membrane Liquid Chromatography

et al. 2017

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In the present work, 79 structurally unrelated analytes were taken into account and their chromatographic retention coefficients, measured by immobilized artificial membrane liquid chromatography (IAM-LC) and by micellar liquid chromatography (MLC) employing sodium dodecyl sulfate (SDS) as surfactant, were determined. Such indexes, along with topological and physicochemical parameters calculated in silico, were subsequently used for the development of blood-brain barrier passage-predictive statistical models using partial least-squares (PLS) regression. Highly significant relationships were observed either using IAM (r (n - 1) = 0.78) or MLC (r (n - 1) = 0.83) derived indexes along with in silico descriptors. This hybrid approach proved fast and effective in the development of highly predictive BBB passage oriented models, and therefore, it can be of interest for pharmaceutical industries as a high-throughput BBB penetration oriented screening method. Finally, it shed new light into the molecular mechanism involved in the BBB uptake of therapeutics.

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Biomimetic chromatography—A novel application of the chromatographic principles

Valkó¹

2022

Analytical Science Advances

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Biomimetic chromatography is the name of the High Performance Liquid Chromatography (HPLC) methods that apply stationary phases containing proteins and phospholipids that can mimic the biological environment where drug molecules distribute. The applied mobile phases are aqueous organic with a pH of 7.4 to imitate physiological conditions that would be encountered in the human body. The calibrated retention of molecules on biomimetic stationary phases reveals a compound's affinity to proteins and phospholipids, which can be used to model the biological and environmental fate of molecules. This technology, when standardised, enables the prediction of in vivo partition and distribution behaviour of compounds and aids the selection of the best compounds for further studies to become a drug molecule. Applying biomimetic chromatographic measurements helps reduce the number of animal experiments during the drug discovery process. New biomimetic stationary phases, such as sphingomyelin and phosphatidylethanolamine, widen the application to the modelling of blood-brain barrier distribution and lung tissue binding. Recently, the measured properties have also been used to predict toxicity, such as phospholipidosis and cardiotoxicity. The aquatic toxicity of drugs and pesticides can be predicted using biomimetic chromatographic data. Biomimetic chromatographic separation methods may also be extended in the future to predict protein and receptor binding kinetics. The development of new biomimetic stationary phases and new prediction models will further accelerate the widespread application of this analytical method.

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Relationships between human intestinal absorption and polar interactions drug/phospholipids estimated by IAM–HPLC.

Cited by 29 publications

References 39 publications

Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers

Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers

Determination of in Vitro and in Silico Indexes for the Modeling of Blood–Brain Barrier Partitioning of Drugs via Micellar and Immobilized Artificial Membrane Liquid Chromatography

Biomimetic chromatography—A novel application of the chromatographic principles

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