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Harvesting Murine Alveolar Macrophages and Evaluating Cellular Activation Induced by Polyanhydride Nanoparticles
Published on: June 8, 2012
Nanoparticles attenuate P-glycoprotein/MDR1 function in A549 human alveolar epithelial cells
Johanna J Salomon1, Carsten Ehrhardt
1School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
Summary
Nanoparticles can impair P-glycoprotein (P-gp) function, affecting drug transport. Particle size and surface properties, like charge, influence this interaction, impacting xenobiotic disposition.
Area of Science:
- Pharmacology
- Nanotechnology
- Cell Biology
Background:
- P-glycoprotein (P-gp)/MDR1 is a key membrane transporter involved in drug disposition and multi-drug resistance.
- Understanding how nanoparticles interact with P-gp is crucial for predicting drug efficacy and toxicity.
Purpose of the Study:
- To investigate the impact of nanoparticulates on P-gp function.
- To identify particle properties that govern these interactions with the P-gp transport system.
Main Methods:
- Rhodamine 123 (Rh123) release studies in A549 cell monolayers.
- Exposure to nanoparticles with varying surface modifications, sizes, and ζ-potentials.
- Cytotoxicity assessment using MTT assay and P-gp expression analysis via Western blot.
Main Results:
- Carboxylated (100 nm), amine-, and sulphate-modified nanoparticles significantly increased cellular retention of Rh123.
- Positively charged amine nanoparticles exhibited higher cytotoxicity.
- Nanoparticles did not disrupt cell membrane integrity, as shown by Western blot.
Conclusions:
- Nanomaterials can attenuate P-gp function, with effects dependent on particle size and surface properties.
- These interactions may influence the disposition of xenobiotics and endogenous substrates.
- Further research is needed to elucidate the precise mechanisms of nanoparticle-P-gp interaction.

