Cancer cell reprogramming is emerging as a promising cancer therapeutic approach that aims to revert malignant cells to a more benign or normal state. Drug repurposing offers an effective strategy to extend the therapeutic potential of existing drugs for new indications, including cancer treatment. However, poor aqueous solubility restricts the therapeutic application of simvastatin (SIM) and piperine (PIP). Cyclodextrin-based inclusion complexation represents a promising method to enhance the solubility and bioavailability of poorly soluble drugs. This study aimed to develop a SIM-PIP co-loaded inclusion complex with methyl-β-cyclodextrin (Mβ-CD) using the freeze-drying technique to improve solubility, dissolution rate, and anticancer activity. SIM-PIP co-loaded inclusion complex was prepared by freeze-drying and characterized through different physicochemical analyses. The cytotoxic activity of SIM, PIP, and their co-loaded inclusion complex was evaluated against HepG2 liver cancer cells using the MTT assay. Furthermore, molecular docking studies were performed to investigate the interactions of SIM and PIP with key molecular targets involved in tumor progression and multidrug resistance, including HMG-CoA reductase, HDAC2, JNK, PI3K, CYP3A4, COX-2, Cathepsin B, and MMP-9. Phase solubility analysis revealed an AL-type curve with a high stability constant and complexation efficiencies. Dissolution studies demonstrated poor release from pure SIM (15.4 ± 0.4 %) and PIP (22.2 ± 1.1 %) after 120 min, whereas the SIM-PIP co-loaded inclusion complex achieved near-complete drug release (PIP: 99.7 ± 4.3 % in 45 min; SIM: 98.4 ± 3.7 % in 60 min). XRD and SEM analyses confirmed the transformation of crystalline SIM and PIP into an amorphous state upon inclusion within the Mβ-CD cavity. Cytotoxicity testing showed that both SIM and PIP possess cytotoxic activity, with the co-loaded inclusion complex exhibiting enhanced potency on the HepG2 cell line. Molecular docking revealed favorable interactions of SIM-PIP with multiple cancer-related targets (HMG-CoA reductase, HDAC2, JNK, PI3K, CYP3A4, COX-2, Cathepsin B, and MMP-9), supporting a potential synergistic effect. In conclusion, the freeze-dried SIM-PIP co-loaded inclusion complex demonstrates a promising drug repurposing strategy to overcome solubility challenges, enhance dissolution, and potentiate therapeutic efficacy by modulating multiple molecular signaling pathways involved in the development of liver cancer cells.
The leakage of oil or the discharge of industrial oily wastewater not only causes environmental hazards but also threatens human health. Traditional oil–water separation methods have the problem of low separation efficiency, poor recyclability. applications. Therefore, it is urgent to develop a high separation efficiency and environmentally friendly treatment method. In this paper, a kind of superhydrophilic-underwater superhydrophobic material was prepared to separate different oil–water mixtures. Pure silicon MCM-48 zeolite seed was synthesized by hydrothermal synthesis. The Cu mesh was used as the substrate, and the superhydrophilic-underwater superoleophobic MCM-48@Cu mesh was prepared by hydrothermal synthesis using MCM-48 zeolite seed crystals for secondary growth. The morphology and underwater contact angle (CA) were analyzed. The surface of MCM-48@Cu mesh had rough nanostructures, and the underwater CA was 155.9 ± 2°. The separation efficiency of the four oil–water mixtures can reach more than 98 %. The oil–water separation performance of MCM-48@Cu mesh for oil–water mixtures was studied, and the separation efficiency for oil–water mixtures reached more than 98 %. MCM-48@Cu mesh had good acid resistance, alkali resistance, salt resistance and good durability.
Biocides in antifouling paints prevent marine organisms from attaching to boat surfaces; however, because they can harm aquatic life, they are strictly regulated. This study presents a novel, eco-friendly approach using biomass-derived activated carbon (AC) from waste Posidonia oceanica seagrass as a carrier matrix for the controlled release of the biocide econea. This approach was compared with commercial AC. Adsorption isotherms confirmed that biocide uptake follows the Freundlich model, indicating favorable multilayer adsorption on heterogeneous surfaces (R 2 = 0.975 for commercial AC and R 2 = 0.962 for P. oceanica AC). ISO 15181-based 45-day release tests demonstrated that P. oceanica AC effectively regulated biocide kinetics, yielding average leaching rates of 0.080, 0.120, and 0.350 μg/cm2/day at 4 %, 10 %, and 45 % loadings respectively. This outperformed or matched the commercial AC results (0.092, 0.188, and 0.295 μg/cm2/day). The Environmental Risk Assessment revealed that, while risk characterization ratio (RCR) values exceeded 1 within enclosed marinas, they remained safely below 1 in the surrounding open waters. 45-day Aegean Sea field trials confirmed effective biofouling inhibition. In practice, utilizing endemic seagrass waste provides a dual solution: it controls the release of toxic biocides into marine ecosystems thereby satisfying regulatory standards, while delivering long-term antifouling efficacy via a sustainable, cost-effective carrier matrix.
Bisoprolol fumarate (BF), a selective β 1-adrenergic blocker, offers favorable clinical outcomes and pharmacological stability, particularly in its fumarate salt form which enhances aqueous solubility. Accurate quantification of bisoprolol fumarate in pharmaceutical formulations is essential for quality control. Ultra-Performance Liquid Chromatography (UPLC) is preferred for this purpose due to its high resolution, reduced solvent use, and faster analysis time. This study aimed to develop and validate a robust, ecologically sustainable UPLC method for bisoprolol fumarate using a Quality by Design (QbD) approach. A 32 full factorial design was applied to optimize two critical factors: flow rate and column temperature. The optimized chromatographic conditions were a column temperature of 21.1 °C and a flow rate of 0.129 mL/min, using a mobile phase of acetonitrile and 0.1 % formic acid (30:70 v/v). Under these conditions, bisoprolol fumarate was eluted at a retention time of 2.025 ± 0.003 min. The method was validated according to ICH guidelines, demonstrating excellent linearity, accuracy, precision, and robustness. This optimized UPLC method is suitable for routine analysis of bisoprolol fumarate and aligns with green analytical principles due to its minimal solvent use and rapid performance.
Density functional theory (DFT) calculations were performed to investigate the electronic effects of C6 substitution on the nicotinamide (NA) scaffold. Geometry optimizations, frontier molecular orbital analysis, conceptual DFT descriptors, and molecular electrostatic potential (MEP) analyses were employed to establish structure–property relationships for selected electron-donating (CH3 and NH2) and electron-withdrawing (NO2) substituents. The electronic properties of NA were strongly influenced by substituent character. The weak electron-donating CH3 group induced only minor changes relative to the parent molecule, whereas the NH2 and NO2 substituents produced noticeable variations in frontier orbital energies, dipole moments, and charge distribution. Among the investigated derivatives, the NO2-substituted system exhibited the smallest HOMO–LUMO gap, the highest dipole moment, and the highest electrophilicity, indicating enhanced charge separation and electron-accepting ability. Qualitative MEP analysis, further supported by the molecular polarity index (MPI), confirmed substituent-dependent redistribution of electrostatic potential across the molecular surface. Overall, the combined analyses demonstrate that C6 substitution provides a systematic approach for tuning the electronic structure of nicotinamide and establish consistent structure–property relationships that may facilitate the rational design of related functional derivatives.
