Herein,
we report the use of sequential layer-by-layer (LbL) assembly
to design nanostructured films made of recombinant bacterial membrane
fractions (MF), which overexpress cytochrome P450 (CYP) and cytochrome
P450 reductase. The ability to incorporate MF in LbL multilayered
films is demonstrated by an in situ quartz crystal microbalance with
dissipation monitoring using poly-
l
-lysine or poly-
l
-ornithine as a polycation. Results show that MF preserve a remarkable
CYP1A2 catalytic property in the adsorbed phase. Moreover, atomic
force microscopy images reveal that MF mostly adopt a flattened conformation
in the adsorbed phase with an extensive tendency to aggregate within
the multilayered films, which is more pronounced when increasing the
number of bilayers. Interestingly, this behavior seems to enhance
the ability of embedded MF to remain active after repeated uses. The
proposed strategy constitutes a practical alternative for the immobilization
of active CYP enzymes. Besides their fundamental interest, MF-based
multilayers are useful nano-objects for the creation of new biomimetic
reactors for the assessment of xenobiotic metabolism.
Numerous dermal contact products, such as drugs or cosmetics, are applied on the skin, the first protective barrier to their entrance into the organism. These products contain various xenobiotic molecules that can penetrate the viable epidermis. Many studies have shown that keratinocyte metabolism could affect their behavior by biotransformation. While aiming for detoxification, toxic metabolites can be produced. These metabolites may react with biological macromolecules often leading to sensitization reactions. After passing through the epidermis, xenobiotics can reach the vascularized dermis and therefore be bioavailable and distributed into the entire organism.
To highlight these mechanisms, dermatokinetics, based on the concept of pharmacokinetics, has been developed recently. It provides information on the action of xenobiotics that penetrate the organism through the dermal route.
The purpose of this review is first to describe and synthesize the dermatokinetics mechanisms to consider when assessing the absorption of a xenobiotic through the skin. We focus on skin absorption and specifically on skin metabolism, the two main processes involved in dermatokinetics. In addition, experimental models and methods to assess dermatokinetics are described and discussed to select the most relevant method when evaluating, in a specific context, dermatokinetics parameters of a xenobiotic. We also discuss the limits of this approach as it is notably used for risk assessment in the industry where scenario studies generally focus only on one xenobiotic and do not consider interactions with the rest of the exposome. The hypothesis of adverse effects due to the combination of chemical substances in contact with individuals and not to a single molecule are being increasingly studied and embraced in the scientific community.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.