Parabens Permeation through Biological Membranes: A Comparative Study Using Franz Cell Diffusion System and Biomimetic Liquid Chromatography

Abstract

Parabens (PBs) are used as preservatives to extend the shelf life of various foodstuffs, and pharmaceutical and cosmetic preparations. In this work, the membrane barrier passage potential of a subset of seven parabens, i.e., methyl-, ethyl-, propyl- isopropyl, butyl, isobutyl, and benzyl paraben, along with their parent compound, p-hydroxy benzoic acid, were studied. Thus, the Franz cell diffusion (FDC) method, biomimetic liquid chromatography (BLC), and in silico prediction were performed to evaluate the soundness of both describing their permeation through the skin. While BLC allowed the achievement of a full scale of affinity for membrane phospholipids of the PBs under research, the permeation of parabens through Franz diffusion cells having a carbon chain > ethyl could not be measured in a fully aqueous medium, i.e., permeation enhancer-free conditions. Our results support that BLC and in silico prediction alone can occasionally be misleading in the permeability potential assessment of these preservatives, emphasizing the need for a multi-technique and integrated experimental approach.

Keywords: Franz cell; chromatography approach; immobilized artificial membrane; investigative toxicology; lipophilicity; parabens; skin.

Figure 1

Chemical structure of parabens under investigation.

Figure 2

Relationship with phospholipophilicity data achieved on IAM.PC.MG and IAM.PC.DD2 stationary phases.

Figure 3

Relationship between Log Kp values achieved from SwissADME^® software and log kw ^IAM.MG (A) and logkw ^IAM.DD2 (B) values achieved by IAM chromatography. A good relationship is observed, demonstrating that IAM experimental data of affinity for phospholipid agree with skin permeation data.