Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study was to investigate the possibility of improving the solubility and the bioavailability of NIM via complexation with polysaccharide arabinogalactan (AG), disodium salt of glycyrrhizic acid (Na₂GA), hydroxypropyl-β-cyclodextrin (HP-β-CD) and MgCO₃. Solid dispersions (SD) have been prepared using a mechanochemical technique. The physical properties of nimesulide SD in solid state were characterized by differential scanning calorimetry and X-ray diffraction studies. The characteristics of the water solutions which form from the obtained solid dispersions were analyzed by reverse phase and gel permeation HPLC. It was shown that solubility increases for all complexes under investigation. These phenomena are obliged by complexation with auxiliary substances, which was shown by ¹H-NMR relaxation methods. The parallel artificial membrane permeability assay (PAMPA) was used for predicting passive intestinal absorption. Results showed that mechanochemically obtained complexes with polysaccharide AG, Na₂GA, and HP-β-CD enhanced permeation of NIM across an artificial membrane compared to that of the pure NIM. The complexes were examined for anti-inflammatory activity on a model of histamine edema. The substances were administered per os to CD-1 mice. As a result, it was found that all investigated complexes dose-dependently reduce the degree of inflammation. The best results were obtained for the complexes of NIM with Na₂GA and HP-β-CD. In noted case the inflammation can be diminished up to 2-fold at equal doses of NIM.

Background: Epilepsy is a prevalent and disabling neurological condition characterized by recurrent seizures. Approximately 50% of adults with active epilepsy have at least one comorbidity and they are at a greater risk of premature death than the general population. Gentiopicroside (Gent) is a primary component of Gentiana macrophylla Pall. that has been shown to have diverse pharmacological properties. However, its role in epileptic seizures in adult mice and its underlying mechanism of action remain obscure. We aimed to explore the anti-epileptic effect and mechanism of Gent on lithium/pilocarpine (Pilo)-induced epilepsy seizures in mice. Methods: In this study, we established a lithium/Pilo-induced epilepsy model, and Gent was first given to mice 30 min before Pilo administration. Then, we detected behavioral and histopathological changes through electrocorticographic (ECoG) measurements, Nissl staining, Fluoro-Jade B (FJB) staining, and immunohistochemical staining. We then used molecular biology techniques, such as Western blotting, quantitative polymerase chain reaction (qPCR) analysis, and the enzyme-linked immunosorbent assay (ELISA) to investigate the mechanisms of Gent in lithium/Pilo-induced epileptic seizures in mice and lipopolysaccharide (LPS)-induced inflammatory astrocytes. Results: We confirmed that Gent could prevent abnormal ECoG activity, behavioral changes, and neurodegeneration. Subsequently, we found Gent could downregulate the factors that could promote apoptosis (i.e., the NR2B/CaMKII/CREB signaling cascade) and neuroinflammatory-related factors (i.e., the TLR4/NF-κB signaling cascade). Conclusions: Gent could be a potential therapeutic agent for epilepsy, offering possibilities for both prevention and treatment. Our research establishes a preliminary experimental framework for ongoing studies into Gent’s efficacy as a treatment for epilepsy.