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Related Concept Videos

Methods for Studying Drug Absorption: In vitro01:16

Methods for Studying Drug Absorption: In vitro

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In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
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Multilayer spheroids to quantify drug uptake and diffusion in 3D.

Toni-Marie Achilli1, Stephanie McCalla, Julia Meyer

  • 1Department of Molecular Pharmacology, Physiology and Biotechnology, ‡Center for Biomedical Engineering, and §School of Engineering, Brown University , Providence, Rhode Island 02912, United States.

Molecular Pharmaceutics
|March 20, 2014
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Summary

This study introduces a 3D spheroid model to quantify drug diffusion and uptake. The model effectively assesses drug transport mechanisms, aiding in the development of predictive drug discovery tools.

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Area of Science:

  • Pharmacology
  • Cell Biology
  • Biophysics

Background:

  • Developing predictive in vitro models for drug discovery is crucial.
  • Quantitative assessment of drug uptake and diffusion is needed to evaluate drug efficacy and toxicity.

Purpose of the Study:

  • To develop and validate a 3D multilayer spheroid model for quantitative analysis of drug uptake and diffusion.
  • To investigate the roles of P-glycoprotein (Pgp) and gap junction intercellular communication (GJIC) in drug transport using this model.

Main Methods:

  • Utilized a 3D multilayer spheroid model with fluorescent calcein-AM.
  • Quantitatively studied calcein uptake and inward diffusion in various cell types.
  • Assessed the effects of Pgp overexpression, Pgp inhibitors (verapamil, loperamide, cyclosporin A), and a GJIC inhibitor (carbenoxolone).

Main Results:

  • Spheroids accumulated calcein, with uptake modulated by Pgp activity.
  • Calcein accumulation decreased in Pgp-overexpressing spheroids and increased with Pgp inhibitors.
  • Inward diffusion of calcein was dependent on GJIC and inhibited by carbenoxolone.
  • Verapamil and loperamide inhibited both Pgp and GJIC, while cyclosporin A only inhibited Pgp.

Conclusions:

  • The 3D spheroid model provides a quantitative platform for studying drug transport.
  • The model accurately reflects in vivo barriers to drug uptake and diffusion.
  • This approach can enhance the predictive power of drug discovery models.