The development of novel oral drug delivery systems is an expanding area of research and both new approaches for improving their efficacy and the investigation of their potential toxicological effect are crucial and should be performed in parallel. Polystyrene nanoparticles (NPs) have been used for the production of diagnostic and therapeutic nanosystems, are widely used in food packaging, and have also served as models for investigating NPs interactions with biological systems. The mucous gel layer that covers the epithelium of the gastrointestinal system is a complex barrier-exchange system that it is mainly constituted by mucin and it constitutes the first physical barrier encountered after ingestion. In this study, we aimed to investigate the effect of polystyrene NPs on mucin and its potential role during NP–cell interactions. For this purpose, we evaluated the interaction of polystyrene NPs with mucin in dispersion by dynamic light scattering and with a deposited layer of mucin using a quartz crystal microbalance with dissipation technology. Next, we measured cell viability and the apoptotic state of three enterocyte-like cell lines that differ in their ability to produce mucin, after their exposure to the NPs. Positive charged NPs showed the ability to strongly interact and aggregate mucin in our model. Positive NPs affected cell viability and induced apoptosis in all cell lines independently of their ability of produce mucin.

Pancreatic cancer is characterized by one of the lowest five-year survival rates. In search for new treatments, some studies explored several metal complexes as potential anticancer drugs. Therefore, we investigated three newly synthesized oxidovanadium(IV) complexes with 2-methylnitrilotriacetate (bcma³⁻), N-(2-carbamoylethyl)iminodiacetate (ceida³⁻) and N-(phosphonomethyl)-iminodiacetate (pmida⁴⁻) ligands as potential anticancer compounds using pancreatic cancer cell lines. We measured: Cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and lactate dehydrogenase (LDH) assay; antiproliferative activity by bromodeoxyuridine BrdU assay; reactive oxygen species (ROS) generation and cell cycle analysis by flow cytometry; protein level by Western blot and cellular morphology by confocal laser scanning microscopy. The results showed that these oxidovanadium(IV) complexes were cytotoxic on pancreatic cancer cells (PANC-1 and MIA PaCa2), but not on non-tumor human immortalized pancreas duct epithelial cells (hTERT-HPNE) over the concentration range of 10–25 μM, following 48 h incubation. Furthermore, molecular mechanisms of cytotoxicity of [4-NH₂-2-Me(Q)H][VO(bcma)(H₂O)]2H₂O (T1) were dependent on antiproliterative activity, increased ROS generation, cell cycle arrest in G2/M phase with simultaneous triggering of the p53/p21 pathway, binucleation, and induction of autophagy. Our study indicates that oxidovanadium(IV) coordination complexes containing 2-methylnitrilotriacetate ligand are good candidates for preclinical development of novel anticancer drugs targeting pancreatic cancer.

Matrix metalloproteinase-9 is upregulated in inflammatory bowel disease. Barbiturate nitrate hybrid compounds have been designed to inhibit MMP secretion and enzyme activity. In this study, we investigated the mechanism of action of barbiturate-nitrate hybrid compounds and their component parts using models of intestinal inflammation in vitro. Cytokine-stimulated Caco-2 cells were used in all in vitro experiments. The NO donors SNAP and DETA-NONOate were used to study the effect of NO on MMP-9 mRNA. Mechanistic elucidation was carried out using the soluble guanylate cyclase (sGC) inhibitor, ODQ, and the cGMP analogue, 8-Bromo-cGMP. Further experiments were carried out to elucidate the role of NF-κB. NO donors exerted an inhibitory effect on MMP-9 mRNA in cytokine-stimulated cells. While the non-nitrate barbiturates had a limited effect on MMP-9 expression, the hybrid compounds inhibited MMP-9 expression through its NO-mimetic properties. No effect could be observed on mRNA for MMP-1 or MMP-2. The sGC inhibitior, ODQ, abolished the nitrate-barbiturate inhibition of MMP-9 gene expression, an effect which was reversed by 8-Br-cGMP. This study shows that the barbiturate scaffold is suitable for hybrid design as an MMP-9 inhibitor in cytokine-stimulated Caco-2 cells. The inhibition of MMP-9 levels was largely mediated through a reduction in its mRNA by a sGC/cGMP pathway mediated mechanism.

Research indicates that appropriately designed educational interventions may impact positively on moral reasoning competencies development (MRCD) as measured by a psychometric measure known as the Defining Issues Test (DIT). However, findings include that educational interventions intended to impact on MRCD do not consistently promote measurable pre-post development. This paper reviews the theoretical background to the use of educational interventions to impact on MRCD, and spotlights how underpinning Neo-Kohlbergian theory might inform the design of an intervention in order to optimise impact on MRCD. Findings indicate that peer debate - regarding ethical concepts in profession-specific dilemma scenarios, what action(s) might be taken and how ‘less than ideal’ action options might be justified - is essential. Five examples of an adapted format of ‘Neo-Kohlbergian’ profession-specific ‘intermediate concept measures’ (ICMs) are included and were integrated into a 16 week blended learning educational intervention in a manner that promoted repeated exposure to peer debate regarding dilemmas, and the educational intervention design was trialled in a study with 27 volunteer community pharmacists in Ireland. An overview of the design, development and delivery of the intervention is provided. The paper concludes with recommendations for further development of the ‘idea’. Conflict of Interest: None Type: Idea Paper

Graphene oxide’s (GO) intravascular applications and biocompatibility are not fully explored yet, although it has been proposed as an anticancer drug transporter, antibacterial factor or component of wearable devices. Bivalent cations and the number of particles’ atom layers, as well as their structural oxygen content and pH of the dispersion, all affect the GO size, shape, dispersibility and biological effects. Bovine serum albumin (BSA), an important blood plasma protein, is expected to improve GO dispersion stability in physiological concentrations of the precipitating calcium and magnesium cations to enable effective and safe tissue perfusion. Methods: Four types of GO commercially available aqueous dispersions (with different particle structures) were diluted, sonicated and studied in the presence of BSA and physiological cation concentrations. Nanoparticle populations sizes, electrical conductivity, zeta potential (Zetasizer NanoZS), structure (TEM and CryoTEM), functional groups content (micro titration) and dispersion pH were analyzed in consecutive preparation stages. Results: BSA effectively prevented the aggregation of GO in precipitating concentrations of physiological bivalent cations. The final polydispersity indexes were reduced from 0.66–0.91 to 0.36–0.43. The GO-containing isotonic dispersions were stable with the following Z-ave results: GO1 421.1 nm, GO2 382.6 nm, GO3 440.2 nm and GO4 490.1 nm. The GO behavior was structure-dependent. Conclusion: BSA effectively stabilized four types of GO dispersions in an isotonic dispersion containing aggregating bivalent physiological cations.