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Related Concept Videos

Cellular Membranes and Drug Transport01:24

Cellular Membranes and Drug Transport

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.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Drug Distribution: Tissue Binding01:21

Drug Distribution: Tissue Binding

Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
For...
Assembly of the Lipid Bilayer in the ER01:28

Assembly of the Lipid Bilayer in the ER

Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
Eukaryotic Compartmentalization01:37

Eukaryotic Compartmentalization

One of the distinguishing features of eukaryotic cells is that they contain membrane-bound organelles, such as the nucleus and mitochondria, that carry out specialized functions. Since biological membranes are only selectively permeable to solutes, they help create a compartment with controlled conditions inside an organelle. These microenvironments are tailored to the organelle's specific functions and help isolate them from the surrounding cytosol.
For example, lysosomes in the animal cells...
Eukaryotic Compartmentalizations01:46

Eukaryotic Compartmentalizations

One of the distinguishing features of eukaryotic cells is that they contain membrane-bound organelles, such as the nucleus and mitochondria, that carry out specialized functions. Since biological membranes are only selectively permeable to solutes, they help create a compartment with controlled conditions inside an organelle. These microenvironments are tailored to the organelle's specific functions and help isolate them from the surrounding cytosol.
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ER Retrieval Pathway01:45

ER Retrieval Pathway

In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...

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Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier
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Published on: February 8, 2017

Cellular membranes function as a storage compartment for celecoxib.

Thorsten J Maier1, Susanne Schiffmann, Ivonne Wobst

  • 1Pharmazentrum Frankfurt/ZAFES, Goethe-University, Frankfurt am Main, Germany.

Journal of Molecular Medicine (Berlin, Germany)
|July 31, 2009
PubMed
Summary
This summary is machine-generated.

Celecoxib accumulates in human cells, reaching higher intracellular concentrations than other coxibs. This accumulation, due to integration into cell membranes, may explain its interaction with non-COX-2 targets despite low plasma levels.

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Area of Science:

  • Pharmacology
  • Cell Biology
  • Biochemistry

Background:

  • Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, treats inflammation and pain.
  • High doses of celecoxib show potential in preventing colorectal cancer by affecting non-COX-2 proteins.
  • In vitro effective concentrations of celecoxib exceed in vivo plasma levels, suggesting intracellular accumulation.

Purpose of the Study:

  • To investigate whether celecoxib accumulates in human cells.
  • To compare intracellular celecoxib concentrations with other coxibs.
  • To elucidate the mechanism and consequences of celecoxib's intracellular accumulation.

Main Methods:

  • Determination of intracellular celecoxib concentrations using liquid chromatography tandem mass spectrometry.
  • Analysis of celecoxib's integration into cellular membranes via nuclear Overhauser spectroscopy/nuclear magnetic resonance.
  • Assessment of celecoxib's effect on plasma membrane integrity and COX-2 inhibitory potency in various cell types.

Main Results:

  • Intracellular celecoxib concentrations were five- to tenfold higher than other coxibs in multiple human tumor and non-tumor cell types.
  • Celecoxib integrates into cellular phospholipid membranes, leading to its accumulation.
  • Accumulated celecoxib disturbed plasma membrane integrity and enhanced COX-2 inhibition in specific cell lines.

Conclusions:

  • Intracellular accumulation of celecoxib is unique among the studied coxibs.
  • This accumulation in human cells provides a potential molecular basis for celecoxib's interaction with non-COX-2 targets in vivo.
  • The findings offer new insights into celecoxib's pharmacological profile and therapeutic potential.