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Related Concept Videos

Transcellular Transport of Solutes01:23

Transcellular Transport of Solutes

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Transcellular transport of solutes is the movement of substances like monosaccharides and amino acids through polarized cells. This transport mechanism is primarily seen in epithelial and endothelial cells aided by membrane transport proteins such as channels and transporters. The tight junctions between these cells confine the membrane proteins to the two sides of the cell. The epithelial cells have distinct apical and basolateral domains. In contrast, the endothelial cells show the luminal...
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The Significance of Membrane Transport01:44

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The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
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Cellular Membranes and Drug Transport01:24

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Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
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Membrane Transporters01:31

Membrane Transporters

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Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
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Introduction to Membrane Traffic01:44

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The ER, Golgi apparatus, endosomes, and lysosomes work in tandem to modify, sort, and package proteins and lipids. An integrated membrane trafficking network facilitates the back and forth shuttling of molecules within different organelles in the same cell or across the cell membrane.
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Facilitated Diffusion01:16

Facilitated Diffusion

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The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

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Lessons in Transcellular Membrane Transport Re-Learned.

Michael M Hann1

  • 1Medicinal Sciences and Technologies, GSK Medicine's Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK.

Journal of Pharmaceutical Sciences
|November 4, 2020
PubMed
Summary
This summary is machine-generated.

We studied drug concentrations in HeLa cells, finding that quantitative structure-activity relationship (QSAR) bell-shaped models using logP and -logP^2 terms align with our results, aided by Immobilised Artificial Membrane chromatography.

Keywords:
BioavailabilityBiomimetic(s)Biophysical model(s)Free fractionMembrane transportQuantitative structure–activity relationship(s) (QSAR)

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Area of Science:

  • Pharmacology and Drug Discovery
  • Biophysical Chemistry
  • Cell Biology

Background:

  • Understanding drug behavior in cells is crucial for drug discovery.
  • Quantitative Structure-Activity Relationships (QSAR) are vital for predicting drug properties.
  • Traditional Artificial Membrane Permeability Assays (aMPA) have limitations.

Purpose of the Study:

  • To measure total and free drug concentrations in HeLa cells for numerous drug discovery compounds.
  • To investigate the applicability of Hansch's QSAR models (bell-shaped using logP and -logP^2) to experimental data.
  • To compare a novel measurement approach with established aMPA methods.

Main Methods:

  • Measurement of total and free drug concentrations in HeLa cells.
  • Utilizing an approach inspired by Professor Per Arturrsson's work.
  • Employing chromatographic Immobilised Artificial Membrane (IAM) measurements.
  • Analysis using Quantitative Structure-Activity Relationship (QSAR) principles.

Main Results:

  • Observed a bell-shaped relationship between drug properties (logP, -logP^2) and concentration, consistent with Hansch's QSAR models.
  • Demonstrated the utility of IAM chromatography in interpreting these QSAR relationships.
  • Identified key differences between the novel measurement approach and standard aMPA.

Conclusions:

  • Hansch's QSAR models, incorporating logP and -logP^2, are applicable to experimental drug concentration data in HeLa cells.
  • Chromatographic IAM measurements provide valuable insights into drug behavior and QSAR interpretation.
  • The study highlights an alternative, potentially more informative, method for assessing drug-cell interactions compared to aMPA.