Introduction. Among nanoparticles (NPs) of metal compounds, PbS and Fe2O3 NPs have become widely used in various fields of economy, medicine, pharmacy, cosmetology. The danger of their exposure is related to the physical and chemical properties of metals and the size of the NPs. The results of the previously conducted morphofunctional studies of the skin during long-term dermal applications (3 months) of PbS NPs (12.5 nm and 100 nm) and Fe2O3 NPs (19 nm and 75 nm) made it possible to reveal the different nature of barrier damage structures of the epidermis and dermis depending on the compounds of various metals and the sizes of their NPs. Early and characteristic signs of structural changes were demonstrated already within 1 month after exposure to NPs of small-sized lead and iron compounds (12.5 nm and 19 nm, respectively). These changes create more favorable conditions for their penetration through the skin. To date, the mechanism of this process remains unclear.
The purpose of the study is to determine in a comparative aspect the early (1 month) mechanisms of absorption processes of nanoparticles of metal compounds (PbS, Fe2O3) through the skin after long-term applications (3 months) and the presence of differences in the nature of morpho-functional damage to the barrier structures of the epidermis and dermis.
Research materials and methods.
Male Wistar rats (n=40) were divided into five groups (one control and four experimental). Colloidal solutions of PbS NPs of 12.5 nm and 100 nm size, and Fe2O3 NPs of 19 nm and 75 nm size were applied to intact (excised) skin of experimental rats, 5 days a week for 1 month. The amount was calculated based on 0.001 mol/100 g of rat body weight and skin area was 2 cm². Morphological studies of the skin were performed using generally accepted and special histological and histochemical methods, as well as morphometric parameters of the thickness of all layers of the skin epidermis and the volume of the cells of the basal layer (determination of small and large diameters).
The results. During long-term dermal applications of PbS NP, morphofunctional changes were characterized by changes of the chemical composition of the protein-lipid envelope of stratum corneum corneocytes (the presence of acidic proteins) and a complication of the process of keratinization of the epidermis (atrophy of all layers), which indicates early manifestations of the mechanism of their absorption directly through the epidermis. Dermal applications of Fe2O3 NPs did not cause morphometric changes in the epidermis. The process of keratinization was preserved, but the presence of early dystrophic changes in the cells of the basal layer and small protein crystal-like inclusions in their cytoplasm testify the penetration of Fe2O3 NPs through the upper layers of the epidermis into its basal layer. The absorption of lead and iron NPs through the epidermis into the dermis is primarily determined by their affinity for proteins, which is greater than the action of Fe2O3 NPs. The presence of small granular dense inclusions in the structures of the dermis, in comparison with PbS NPs, is associated with various morphofunctional changes in them. These changes determine the distinct mechanisms of Fe2O3 and PbS NPs absorption into the blood. PbS NPs caused destructive damage to collagen fibrils, type III collagen of the basal plate and muscle fibers with accumulation of acidic proteins in the dermis, which indicates a damage of the mechanical properties of the dermis structures and determines a completely different mechanism of their penetration through it.
Conclusions. Differences in the nature of the morphofunctional changes of the skin during long-term dermal application of PbS and Fe2O3 NPs determine different mechanisms of their penetration. The early mechanism of absorption of PbS NPs directly through the epidermis is determined by a wider spectrum of its morphofunctional damage compared to the action of Fe2O3 NPs. Different mechanisms of the dermal absorption of PbS and Fe2O3 NPs are determined by their physicochemical properties, the size of the nanoparticles, affinity with proteins, and the nature of damage to type III collagen, collagen fibrils, and muscle myofibrils. Increased secretory activity of tissue basophils (hyperplasia, hypertrophy, degranulation) contributes to increased capillary and tissue permeability for PbS and Fe2O3 NPs of small sizes.
Keywords: penetration mechanism, epidermis, dermis, nanoparticles (NPs), iron oxide (Fe2O3), lead sulfide (PbS), acidic proteins, GAG (glycosamine glycans), fibers (collagen, muscle), tissue basophils.
References
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