Study of the potential antipsoriatic effectiveness and safety of the combination of naftalan oil with salicylic acid in cellular test systems

The aim of this work was to evaluate the combination of purified naftalan oil (PNO) with salicylic acid (SA) for topical application as a potential effective antipsoriatic ointment and to study the mechanism of its action using specific in vitro cell models. Material and methods. The effectiveness and safety of the following dosage forms were studied: ointment with 10 % PNO and 3 % SA (PNO-SA), cream with 0.064 % betamethasone dipropionate (BD), and ointment with 3 % SA. Cell viability of original HaCaT human keratinocytes and modified HaCaT/P was determined by colorimetric methods, namely by crystal violet staining or the MTT test method. The level of apoptosis of cells was evaluated by flow cytometry. Production of pro-inflammatory cytokines IL-8 and IL-1β was measured by the ELISA method. Results. It was shown that the sensitivity of cells with a psoriasis-like phenotype (HaCaT/P) to PNO increases statistically significantly compared to control cells, which was confirmed by both the cell viability and the MTT test. to obtain a result with inhibition of cells with psoriasis-like characteristics, HaCaT/P requires a smaller concentration of the drug compared to a similar effect on conditionally normal cells – HaCaT. This may indicate the relative safety of the proposed medicinal product (combination) in parallel with the conditions of its effectiveness concerning pathologically changed cells. The results of flow cytometry showed that the new PNO-SA complex causes a statistically significant increase in the percentage of cells in all phases of apoptosis compared to control cells. Finally, a statistically significant decrease in the production of IL-8 by cells with psoriasis-like characteristics – the HaCaT/P line was shown in the presence of the PNO-SA combination compared with control cells. In addition, there was a significant decrease in the level of IL-8 production in cells in the presence of the combination compared to SA and the comparator BD. However, in terms of its effect on IL-1β production, the PNO-SA combination proved to be inactive. Conclusion. Our proposed combination (PNO-SA), which suppresses pro-inflammatory IL-8 by more than 2 times (by 67.4 %) compared to the control, is a promising potential option for local treatment of psoriatic lesions. We speculate about the future demand of this combination in the clinical setting because along with high efficiency (in terms of viability indicators – the number of living cells, the level of apoptosis) towards pathologically changed keratinocytes, it shows a low toxicity profile towards normal healthy keratinocytes