The purpose of the study was to investigate the stability and biopharmaceutical characteristics of ketoprofen, loaded in polymeric carriers, which were included into a bigel in a semisolid dosage form. The polymer carriers with in situ-included ketoprofen were obtained by emulsifier-free emulsion polymerization of the monomers in aqueous medium or a solution of the polymers used. The morphological characteristics of the carriers, the in vitro release and the photochemical stability of ketoprofen were evaluated. The model with optimal characteristics was included in a bigel formulation. The bigel was characterized in terms of pH, rheological behavior, spreadability, and in vitro drug release. Acute skin toxicity, antinociceptive activity, anti-inflammatory activity, and antihyperalgesic effects of the prepared bigel with ketoprofen-loaded polymer carrier were evaluated. The carriers of ketoprofen were characterized by a high yield and drug loading. The particle size distribution varied widely according to the polymer used, and a sustained release was provided for up to 6 hours. The polymer mixture poly(vinyl acetate) and hydroxypropyl cellulose as a drug carrier, alone or included in the bigel composition, improved the photostability of the drug compared with unprotected ketoprofen. The bigel with ketoprofen-loaded particles provided sustained release of the drug and had optimal rheological parameters. In vivo experiments on the bigel showed no skin inflammation or irritation. Four hours after its application, a well-defined analgesic, anti-inflammatory, and antihyperalgesic effect was registered. The polymer mixture of poly(vinyl acetate) and hydroxypropyl cellulose as a carrier of ketoprofen and the bigel in which it was included provided an enhanced photostability and sustained drug release.

Oxydative stress, anxiety and depression are associated with changes in cytokine levels. Natural products, including individual and combined plant extracts, have the potential to be used in the treatment of neuropsychiatric disorders. The goal of this study is to investigate the effects of two combined plant extracts, rich in flavonoids, on the levels of the cytokines TNF-α, IL-6, and IL-10 in rats subjected to models of acute cold stress and chronic unpredictable stress. The study utilized common medicinal plants such as Valeriana officinalis, Melissa officinalis, Crataegus monogyna, Hypericum perforatum, and Serratula coronata, which were combined in two unique combinations—Antistress I and Antistress II. The compositions of the used extracts were determined by HPLC methods. Pro- and anti-inflammatory cytokines in rats’ serum were measured with Enzyme-linked immunosorbent assay. The results from the acute stress model revealed that the individual extract of Crataegus monogyna decreased levels of TNF-α, while Serratula coronata, Hypericum perforatum, and Valeriana officinalis effectively reduced IL-6 levels. Both combinations, Antistress I and Antistress II, were effective in reducing TNF-α and IL-6 levels, with Antistress II also increasing IL-10 levels. In the chronic stress model, Hypericum perforatum extract decreased the levels of the pro-inflammatory cytokines TNF-α and IL-6, whereas extracts of Serratula coronata and Valeriana officinalis only reduced TNF-α levels. The two combined extracts, Antistress I and Antistress II, decreased TNF-α and IL-6 levels, while Antistress I also reduced the levels of the anti-inflammatory cytokine IL-10. The combinations of plant extracts used in our experiment have not been previously studied or documented in the available literature. However, based on our own experimental results, we can draw the conclusion that the combinations exhibit a more pronounced effect in reducing cytokine levels compared to the individual plant extracts.