Investigating the Phospholipid Effect on the Bioaccessibility of Rosmarinic Acid-Phospholipid Complex through a Dynamic Gastrointestinal in Vitro Model

Phyto-phospholipid complexes have been developed as a common way of improving the oral bioavailability of poorly absorbable phyto-pharmaceuticals; however, the complexation with phospholipids can induce positive or negative effects on the bioaccessibility of such plant-derived active ingredients in different parts of the gastrointestinal tract (GIT). The purpose of this study was to investigate the effects of phospholipid complexation on the bioaccessibility of a rosmarinic acid-phospholipid complex (RA-PLC) using the TNO dynamic intestinal model-1 (TIM-1). Preparation of RA-PLC was confirmed using X-ray diffraction, Fourier-transform infrared spectroscopy, partition coefficient measurement, and Caco-2 monolayer permeation test. Bioaccessibility parameters in different GIT compartments were investigated. Complexation by phospholipids reduced the bioaccessibility of RA in jejunum compartment, while maintaining the ileum bioaccessibility. The overall bioaccessibility of RA-PLC was lower than the unformulated drug, suggesting that the improved oral absorption from a previous animal study could be considered as a net result of decreased bioaccessibility overwhelmed by enhanced intestinal permeability. This study provides insights into the effects of phospholipid on the bioaccessibility of hydrophilic compounds, and analyzes them based on the relationship between bioaccessibility, membrane permeability, and bioavailability. Additionally, TIM-1 shows promise in the evaluation of dosage forms containing materials with complicated effects on bioaccessibility.

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Inositol phosphates: health implications, methods of analysis, and occurrence in plant foods

Journal of Food Bioactives ◽

10.31665/jfb.2018.1126 ◽

2018 ◽

Vol 1 ◽

Cited By ~ 1

Author(s):

Quynh H. Duong ◽

Karen G. Lapsley ◽

Ronald B. Pegg

Keyword(s):

Inositol Phosphates ◽

Negative Effects ◽

Plant Foods ◽

Plant Seeds ◽

Cell Functions ◽

Wide Range ◽

Multiple Cell ◽

The Relationship

Inositol phosphates (InsPs), especially myo-inositol hexakisphosphate (InsP6), are important binders of phosphorus and minerals in plant seeds. However, they have long been considered as anti-nutritional components of plant foods due to their possible negative effects on the absorption of minerals and proteins in mammals. On the other hand, recent findings have found InsPs to be ubiquitous in eukaryote cells and actively participating in multiple cell functions. In vivo and in vitro studies have also documented the preventive potential of these compounds against the development of a wide range of diseases. In light of these findings, interest in the relationship between these compounds and human health has been renewed. It is suggested that the interactions of InsPs with other nutrients in the gut are complex, that the absorption of dietary InsPs might be implied but is not certain, and that the disease fighting capabilities of InsPs hold both promises and limitations. At the same time, the analysis of these compounds in foods and biological samples still faces many challenges, calling for more advanced modification and developments in the future.

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Addition of Optimized Bovine Serum Albumin Level in a High-Throughput Caco-2 Assay Enabled Accurate Permeability Assessment for Lipophilic Compounds

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555219848483 ◽

2019 ◽

Vol 24 (7) ◽

pp. 738-744

Author(s):

Xianmei Cai ◽

Shilpa Madari ◽

Aaron Walker ◽

Anthony Paiva ◽

Ying Li ◽

...

Keyword(s):

Bovine Serum Albumin ◽

Serum Albumin ◽

Bovine Serum ◽

Oral Absorption ◽

Albumin Level ◽

Systematic Evaluation ◽

Lipophilic Compounds ◽

Reliable Assessment ◽

Vitro Model

The Caco-2 permeability assay is a well-accepted in vitro model to evaluate compounds’ potential for oral absorption at early discovery. However, for many lipophilic compounds, no meaningful Caco-2 data could be generated due to their low solubility in assay buffer and/or poor recovery from the assay. In our previous study, we reported an organic catch approach to improve compound recovery. To further reduce compound loss and increase solubility in aqueous buffer, we explored the addition of bovine serum albumin (BSA). However, in contrast to the commonly used BSA level at 4%, a lower level of BSA was selected in an effort to minimize the potential risk of missing the identification of efflux substrates, and to avoid the extensive sample cleanup needed for 4% BSA. Through a systematic evaluation, it was found that 0.5% BSA was effective in enhancing compound solubility and reducing nonspecific binding, which allowed reliable assessment of the permeability and efflux potential for lipophilic compounds. Also, with an optimized sample handling process, no extra sample cleanup was required before liquid chromatography–mass spectrometry (LC-MS) analysis. The implementation of this assay has enabled accurate permeability assessment for compounds that had poor solubility and/or poor mass balance under the non-BSA assay conditions.

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Human Brain Organoids as an In Vitro Model System of Viral Infectious Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2021.792316 ◽

2022 ◽

Vol 12 ◽

Author(s):

Xuan Su ◽

Peng Yue ◽

Jing Kong ◽

Xin Xu ◽

Yu Zhang ◽

...

Keyword(s):

In Vitro Model ◽

Viral Infections ◽

Cns Infection ◽

Great Promise ◽

Zikv Infection ◽

Infection Models ◽

Immunodeficiency Virus ◽

Vitro Model ◽

The Relationship

Brain organoids, or brainoids, have shown great promise in the study of central nervous system (CNS) infection. Modeling Zika virus (ZIKV) infection in brain organoids may help elucidate the relationship between ZIKV infection and microcephaly. Brain organoids have been used to study the pathogenesis of SARS-CoV-2, human immunodeficiency virus (HIV), HSV-1, and other viral infections of the CNS. In this review, we summarize the advances in the development of viral infection models in brain organoids and their potential application for exploring mechanisms of viral infections of the CNS and in new drug development. The existing limitations are further discussed and the prospects for the development and application of brain organs are prospected.

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Development and Characterization of Aspirin-Phospholipid Complex for Improved Drug Delivery

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2010.3.2.7 ◽

2010 ◽

Vol 3 (2) ◽

pp. 940-947 ◽

Cited By ~ 1

Author(s):

A Semalty ◽

M Semalty ◽

D Singh ◽

M S M Rawat

Keyword(s):

In Vitro Dissolution ◽

Molar Ratio ◽

X Ray Diffraction ◽

Phospholipid Complex ◽

Scanning Calorimetry ◽

Dissolution Study ◽

Drug Content ◽

Poorly Soluble ◽

Gi Toxicity

Aspirin (acetylsalicylic acid) is one of the most widely used analgesic. Aspirin is poorly soluble in water and causes gastrointestinal (GI) irritation. To improve the solubility (and hence the bioavailability) and minimize the GI irritation, its complexes with soya-phospholipid-80 % (in 1: 1 molar ratio) were prepared in an organic solvent and evaluated for solubility, drug content, scanning electron microscopy (SEM), FT-IR spectra, X ray diffraction, differential scanning calorimetry (DSC) and in vitro dissolution study. Aspirin-phospholipid complex were found to be disc shaped with rough surface in SEM. Drug content in the complex was found to be 95.6 %. DSC thermograms, XRD and FTIR confirmed the formation of phospholipid complex. Solubility of the prepared complex was found to be improved. Aspirin complex and aspirin showed 90.93 % and 69.42 % of drug release at the end of 10 h in dissolution study in pH 1.2 acid buffer. It was concluded that the phospholipid complex of aspirin may be of potential use for improving the solubility of aspirin and hence its bioavailability. The complexes may also reduce GI toxicity of the drug.

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The Factor V R2 Allele: Risk of Venous Thromboembolism, Factor V Levels and Resistance to Activated Protein C

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613786 ◽

2000 ◽

Vol 83 (02) ◽

pp. 204-208 ◽

Cited By ~ 37

Author(s):

Roger Luddington ◽

Andrew Jackson ◽

Sabapathy Pannerselvam ◽

Karen Brown ◽

Trevor Baglin

Keyword(s):

Venous Thromboembolism ◽

Activated Protein C ◽

Carrier Status ◽

Factor V ◽

Case Control Studies ◽

Apc Resistance ◽

Vitro Model ◽

The Relationship ◽

Independent Model

SummaryCase-control studies have yielded conflicting results regarding the relative risk of venous thromboembolism associated with the factor V R2 allele. We calculated odds ratios in 581 patients and 469 agematched controls. The odds ratio for the R2 allele in patients relative to controls was 1.21 (95% CI 0.84 to 1.74). These results do not support the hypothesis that the R2 allele is a risk factor for venous thromboembolism. There was no relationship between factor V levels and R2 carrier status. Normalised APC sensitivity ratios were not lower in carriers of the R2 allele. In an in vitro model progressive APC resistance was observed with factor V levels of 60% and less but ratios less than 2.4 (equivalent to a normalised ratio of 0.73) did not occur until factor V levels were less than 20%. The relationship between APC resistance and factor V level was not observed in a factor VIII-independent model.

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Senescence and associated blood–brain barrier alterations in vitro

Histochemistry and Cell Biology ◽

10.1007/s00418-021-01992-z ◽

2021 ◽

Author(s):

Ellaine Salvador ◽

Malgorzata Burek ◽

Mario Löhr ◽

Michiaki Nagai ◽

Carsten Hagemann ◽

...

Keyword(s):

Blood Brain Barrier ◽

Intercellular Junctions ◽

In Vitro Models ◽

Brain Barrier ◽

Initial Attempt ◽

Blood Brain ◽

The Central Nervous System ◽

Vitro Model ◽

The Relationship

AbstractProgressive deterioration of the central nervous system (CNS) is commonly associated with aging. An important component of the neurovasculature is the blood–brain barrier (BBB), majorly made up of endothelial cells joined together by intercellular junctions. The relationship between senescence and changes in the BBB has not yet been thoroughly explored. Moreover, the lack of in vitro models for the study of the mechanisms involved in those changes impede further and more in-depth investigations in the field. For this reason, we herein present an in vitro model of the senescent BBB and an initial attempt to identify senescence-associated alterations within.

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A Human 3D In Vitro Model to Assess the Relationship Between Osteoporosis and Dissemination to Bone of Breast Cancer Tumor Cells

Journal of Cellular Physiology ◽

10.1002/jcp.25708 ◽

2017 ◽

Vol 232 (7) ◽

pp. 1826-1834 ◽

Cited By ~ 9

Author(s):

Francesca Salamanna ◽

Veronica Borsari ◽

Silvia Brogini ◽

Paola Torricelli ◽

Simona Cepollaro ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

In Vitro Model ◽

3D In Vitro Model ◽

Cancer Tumor ◽

Vitro Model ◽

The Relationship

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Rosmarinic acid ameliorates the negative effects of salinity in in vitro-regenerated potato explants (Solanum tuberosum L.)

Acta Physiologiae Plantarum ◽

10.1007/s11738-018-2622-y ◽

2018 ◽

Vol 40 (4) ◽

Cited By ~ 3

Author(s):

Hoda Eskandari ◽

Naemah Al-Mansour ◽

Ali Akbar Ehsanpour

Keyword(s):

Solanum Tuberosum ◽

Rosmarinic Acid ◽

Solanum Tuberosum L ◽

Negative Effects

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The influence of downstream arterial perfusion parameters on Doppler pulsatility index and resistance index in an in-vitro perfusion model

VASA ◽

10.1024/0301-1526.35.1.5 ◽

2006 ◽

Vol 35 (1) ◽

pp. 5-10 ◽

Cited By ~ 2

Author(s):

Schmidt ◽

Ockert ◽

Deußen ◽

Schellong

Keyword(s):

Reflection Coefficient ◽

Pulsatility Index ◽

In Vitro Model ◽

Peripheral Resistance ◽

Resistance Index ◽

In Vitro Perfusion ◽

Arterial Perfusion ◽

Vitro Model ◽

The Relationship

Background: To investigate in vitro how downstream perfusion parameters influence pulsatility index (PI), resistance index (RI) and their constituting Doppler velocities. Materials and methods: We analyzed the influence of resistance, compliance, reflection coefficient and input impedance on PI and RI in an in-vitro model of arterial flow. Results: The nominators of PI and RI were determined by resistance. The numerators were determined by compliance and by the reflection coefficient. There were close relationships of PI and RI with resistance under the condition of constant compliance, but not when compliance was variable. Conclusion: PI and RI consist of velocity terms which are independently influenced by different parameters of impedance: compliance, reflection coefficient and resistance. These findings explain the contradictory results reported for the relationship between the indices and peripheral resistance in studies where compliance and reflection effects were not considered.

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