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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Published on: October 17, 2013

Artificial membrane assays to assess permeability.

Bernard Faller¹

¹Novartis Institutes for BioMedical Research, Basel, Switzerland. bernard.faller@novartis.com

Current Drug Metabolism

|November 11, 2008

Summary

Parallel artificial membrane assays (PAMPA) have advanced significantly, offering robust methods for predicting drug absorption and penetration. This review details PAMPA

Area of Science:

Pharmacokinetics and Drug Discovery
Membrane Transport Studies
Biophysical Chemistry

Background:

Artificial membrane assays have become crucial in early drug discovery for predicting pharmacokinetic properties.
Parallel Artificial Membrane Permeability Assay (PAMPA) has gained prominence due to its simplicity and throughput.
Evaluating drug absorption, distribution, metabolism, and excretion (ADME) properties is essential for successful drug development.

Purpose of the Study:

To review the advancements in artificial membrane assay technology over the past decade.
To discuss the widespread adoption and applications of PAMPA in drug discovery.
To compare PAMPA with traditional cell-based assays like Caco-2 and explore new assay dimensions.

Main Methods:

Review of literature on artificial membrane assay development, focusing on PAMPA.

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Analysis of various PAMPA formats for gastrointestinal absorption, blood-brain barrier penetration, and skin permeation.

Discussion of assay improvements, including paracellular models and critical quality factors.

Comparative analysis of PAMPA and Caco-2 permeability.

Introduction of novel applications such as logP measurement and excipient interaction studies.

Main Results:

PAMPA assays are widely utilized for predicting drug permeability across biological barriers.
Recent developments include enhanced PAMPA models incorporating paracellular pathways and improved data quality control.
PAMPA offers a valuable complement to Caco-2 assays, with distinct applications and interpretations.
New assay dimensions enable the assessment of drug solubility, excipient effects, and binding interactions.

Conclusions:

PAMPA technology has evolved significantly, providing reliable and versatile tools for drug property assessment.
The integration of new features expands the utility of artificial membrane assays beyond simple permeability.
Understanding the differences between partition coefficients and permeability is key to interpreting assay results effectively.
Artificial membrane assays, particularly PAMPA, are indispensable in modern drug discovery workflows.