Chemically cross-linked poly(acrylic-co-vinylsulfonic) acid hydrogel for the delivery of isosorbide mononitrate.

We report synthesis, characterization, and drug release attributes of a series of novel pH-sensitive poly(acrylic-co-vinylsulfonic) acid hydrogels. These hydrogels were prepared by employing free radical polymerization using ethylene glycol dimethacrylate (EGDMA) and benzyl peroxide (BPO) as cross-linker and initiator, respectively. Effect of acrylic acid (AA), polyvinylsulfonic acid (PVSA), and EGDMA on prepared hydrogels was investigated. All formulations showed higher swelling at high pHs and vice versa. Formulations containing higher content of AA and EGDMA show reduced swelling, but one with higher content of PVSA showed increased swelling. Hydrogel network was characterized by determining structural parameters and loaded with isosorbide mononitrate. FTIR confirmed absence of drug polymer interaction while DSC and TGA demonstrated molecular dispersion of drug in a thermally stable polymeric network. All the hydrogel formulations exhibited a pH dependent release of isosorbide mononitrate which was found to be directly proportional to pH of the medium and PVSA content and inversely proportional to the AA contents. Drug release data were fitted to various kinetics models. Results indicated that release of isosorbide mononitrate from poly(AA-co-VSA) hydrogels was non-Fickian and that the mechanism was diffusion-controlled

DNA binding, and apoptosis-inducing activities of a β-ionone-derived ester in human myeloid leukemia cells: multispectral and molecular dynamic simulation analyses

Abstract β-Ionone is the end-ring counterpart of β-carotenoids, which are widely found in fruits and vegetables. Recent studies have illustrated the antimetastatic, anti-proliferative, and apoptosis-inducing activities of β-ionone both in vitro and in vivo. We aimed to explore the anti-cancer potency of β-Ionone-derived ester, (E)-4-(2,6,6-trimethylcyclohex-1-enyl) but-3-en-2-ylpyrazine-2-carboxylate (4-TM.P). The cytotoxic effects of the compound on K562 cells were evaluated by MTT assay. The mechanisms of apoptosis induction were investigated by acridine orange/ethidium bromide (AO/EtBr) double staining, cell cycle analysis, and Annexin V/PI staining. Furthermore, the 4-TM.P-DNA interactions have been thoroughly elucidated by various methods, such as ultraviolet–visible spectroscopy, fluorescence assays, viscosity measurements, molecular docking, and dynamic simulation. The MTT cytotoxicity assay revealed that the growth of K562 cells was inhibited by treatment with β-ionone-derived ester, with an IC50 of 25 ± 5.0 µM at 72 h. Morphological studies revealed the occurrence of apoptosis in treated cells, and G0/G1 cell cycle arrest was observed after treatment of the cells with the IC50 value of the compound. Analyses of multi-spectroscopy and viscosity assays revealed that 4-TM.P binds to DNA in the minor groove mode, which was supported by molecular docking studies. The dynamic stability of the complex was also confirmed using molecular dynamic simulation analyses