Parallel Artificial Membrane Permeability Assay (PAMPA) - Is it Better than Caco-2 for Human Passive Permeability Prediction?

Abstract

This review proposes a statistical and qualitative comparison between the main techniques derived from the original PAMPA method and experimental results obtained from Caco-2 and human jejunum. Among them, PAMPA techniques variations developed by some of the most renowned authors on the subject. The comparison is made from 16 common structurally diverse molecules, taking into account mainly membrane lipid composition and incubation conditions. A BCS classification prediction of the studied molecules was also possible to make. Finally, it was possible to raise and prove important previous hypotheses, aside from pointing out the best PAMPA model to predict human data.

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

“…Drug permeability is important, as the ADMET properties (absorption, distribution, metabolism, elimination and toxicity) depend on it [124,214]. The permeability is quantified by the permeability coefficient P (in m s -1 ), and it is Experimentally, Caco-2 cell permeability assays are still the most commonly used assay to determine the permeability in vitro [221]. Despite its high reliability when extrapolated to in vivo absorption, this assay still has several limitations, such as the time-consuming step of cell growth and the associated costs [221].…”

“…The permeability is quantified by the permeability coefficient P (in m s -1 ), and it is Experimentally, Caco-2 cell permeability assays are still the most commonly used assay to determine the permeability in vitro [221]. Despite its high reliability when extrapolated to in vivo absorption, this assay still has several limitations, such as the time-consuming step of cell growth and the associated costs [221]. Therefore, other methods, such as the parallel artificial membrane permeability assay and immobilized artificial membrane (IAM) chromatography, have been used due to their simplicity and speed [128].…”

Utility of models of the gastrointestinal tract for assessment of the digestion and absorption of engineered nanomaterials released from food matrices

“…pH can affect the surface charge of administered NMs, and can be specified to reflect the properties the NMs would display in the various compartments of the GI tract (Reis et al, 2010). Artificial membrane models could offer high-throughput screening of passive transcellular permeability.…”

Skin PAMPA: Application in practice

“…In most cases, the main goal was to determine permeability as kinetic parameter of pure compounds in early stage of drug discovery without any formulation effect. Most of the protocols was developed to satisfy this need, therefore buffer solutions at various pH with 0.5-1(-5) % DMSO was studied as donor solution and pure pH = 7.4 buffer as acceptor solution [16]. Donor concentration was selected according to the physico-chemical (solubility, pK a , logP) parameters of the compounds and permeability was calculated as the main parameter for comparison.…”