Lower doses of capsaicin (8-methyl-N-vanillyl-6-nonenamide) have the potential to serve as an anticancer drug, however, due to its pungency, irritant effect, poor water solubility and high distribution volume often linked to various off-target effects, its therapeutic use is limited. This study aimed to determine the biodistribution and anticancer efficacy of capsaicin loaded solid lipid nanoparticles (SLNs) in human hepatocellular carcinoma in vitro. In this study, SLNs of stearic acid loaded with capsaicin was formulated by the solvent evaporation-emulsification technique and were instantly characterized for their encapsulation efficiency, morphology, loading capacity, stability, particle size, charge and in vitro drug release profile. Synthesized SLNs were predominantly spherical, 80 nm diameter particles that proved to be biocompatible with good stability in aqueous conditions. In vivo biodistribution studies of the formulated SLNs showed that 48 h after injection in the lateral tail vein, up to 15% of the cells in the liver, 1.04% of the cells in the spleen, 3.05% of the cells in the kidneys, 3.76% of the cells in the heart, 1.31% of the cells in the lungs and 0% of the cells in the brain of rats were determined. Molecular docking studies against the identified targets in HepG2 cells showed that the capsaicin is able to bind Abelson tyrosine-protein kinase, c-Src kinase, p38 MAP kinase and VEGF-receptor. Molecular dynamic simulation showed that capsaicin-VEGF receptor complex is highly stable at 50 nano seconds. The IC50 of capsaicin loaded SLNs in HepG2 cells in vitro was 21.36 μg × ml−1. These findings suggest that capsaicin loaded SLNs are stable in circulation for a period up to 3 d, providing a controlled release of loaded capsaicin and enhanced anticancer activity.

Targeted drug delivery systems are a promising field of research. Nano-engineered material-mediated drug delivery possesses remarkable potential for the treatment of various malignancies. Here, folic acid (FA)-conjugated bovine serum albumin (BSA) nanoparticles (NPs) were used to encapsulate myricetin (Myr). Subsequently, the delivery of Myr via naturally overexpressed folate receptor (FR) to FR-positive breast cancer cells was studied. Myr-loaded BSA NPs were assembled by modified desolvation cross-linking technique. An FA-conjugated carrier, N-hydroxysuccinimide (NHS)-FA ester, was successfully synthesized. Its functional and structural characteristics were confirmed by ultraviolet, Fourier-transform infrared, and proton nuclear magnetic resonance spectroscopy. Biocompatible FA-conjugated, Myr-loaded BSA NPs (FA-Myr-BSA NPs) were successfully formulated using a carbonate/bicarbonate buffer. Their morphology, size, shape, physiological stability, and drug release kinetics were studied. Molecular docking studies revealed that FA-Myr-BSA NPs readily bound non-covalently to folate receptors and facilitated active drug endocytosis. FA-Myr-BSA NPs could trigger fast release of Myr in an acidic medium (pH 5.4), and showed high biocompatibility in a physiological medium. FA-Myr-BSA NPs effectively decreased the viability of MCF-7 cells after 24 h with 72.45 μg ml−1 IC50 value. In addition, FA-Myr-BSA NPs enhanced the uptake of Myr in MCF-7 cells. After incubation, a typical apoptotic morphology of condensed nuclei and distorted membrane bodies was observed. The NPs also targeted mitochondria of MCF-7 cells, significantly increasing reactive oxygen species release and contributing to the loss of mitochondrial membrane integrity. The observed results confirm that the newly developed FA-Myr-BSA NPs can serve as a potential carrier for Myr to increase the anticancer activity of this chemotherapeutic.

1. Numerous studies have tested the combined effect of the threat of predation by fish and low oxygen concentrations on the phenotypic plasticity of Daphnia.These studies assessed the trade-off between minimising predation risk and the negative effects of oxygen deficiencies in the context of depth selection behaviour. We tested whether this trade-off also affects physiological and life history traits. We expected an interactive effect between the threat of fish predation and low oxygen concentrations, such, that the net effect of both stressors would be antagonistic (lower than the sum of each of the stressors acting separately), rather than additive (or synergistic) on the majority of traits investigated, but we predicted synergistic effects on heat shock proteins (HSPs). 2. To test this, we performed life table experiments in different oxygen concentrations (normoxia and hypoxia) and levels of predation threat (the presence and absence of fish kairomones) on HSP70 and putative HSP110, haemoglobin concentration and life history traits with small-bodied Daphnia galeata and large-bodied Daphnia pulex originating from waterbodies where there were different risks of fish predation. 3. As predicted, the net effect of both stressors was antagonistic for most of the physiological and ecological variables studied. The presence of kairomones resulted in decreased body size of adults, egg size, egg size in relation to brood chamber volume, and in increased clutch size in relation to body size. These effects were weaker in hypoxia than in normoxia, which may suggest an existence of adaptive responses caused by a lower perceived risk in hypoxia than in normoxia, as the foraging abilities of fish are limited by oxygen deficiencies. 4. The presence of kairomones hampered the production of haemoglobin in hypoxia for the clones of larger-bodied species, which suggests the existence of a trade-off between reduced visibility under positive-size selective predation risk and increased efficiency of oxygen transport to body tissues. The presence of kairomones and hypoxia resulted in an increased level of putative HSP110, and the effect of kairomones was stronger in hypoxia than in normoxia. More complex results were obtained for the effect of both stressors on the level of HSP70. | 2205 WILCZYNSKI et al.

Artificial light at night may affect mortality risk in prey from visually oriented predators because the effect of the artificial light spectrum may differ for a predator's visual prey detection and for prey evasiveness. To test this, we conducted two types of experiment. First, we assessed the reaction distance and swimming speed of juvenile rudd (Scardinius erythrophthalmus) allowed to forage on juvenile Daphnia pulex × pulicaria under three artificial light sources: halogen, high pressure sodium (HPS), and metal halide bulbs, at the same light intensity. Second, we assessed the evasiveness of D. pulex × pulicaria under the same artificial light sources and in darkness (as a control), in the presence and absence of chemical information on predation risk (kairomones) of juvenile rudd. We found that while both reaction distance and swimming speed of fish was greater under halogen compared to HPS, and similar under metal halide light compared to halogen and HPS, the evasiveness of Daphnia was greater under halogen and HPS-generated light than under metal halide light. The results suggest a possible mismatch of Daphnia's behavioural response under metal halide light to predicted predation risk, and thus a possible threat to predator-prey balance in a lake ecosystem.

The vertical distribution of planktonic animals, such as Daphnia, in overlapping gradients of food concentration and risk of visual predation should depend on Daphnia population density and should be the result of the group effect of optimizing decisions taken by each individual (juvenile or adult), trading-off a high growth rate to low mortality risk. We tested this hypothesis by comparing the theoretical distributions from simulations based on an experimentally parameterized, optimizing individual-based model (consistent with the assumptions of the concept of the interference ideal free distribution with costs) with distributions observed in laboratory experiments. The simulations were generated for two scenarios, where the shape of the functional response of fish is consistent with either type II or III. The results confirmed the hypothesis. The greatest similarity of the distributions obtained in the experiments and simulations was found for the simulations based on the scenario assuming the type III rather than type II for both age classes of Daphnia. This was consistent with the results of the experiments for the model parameterization, which revealed the type III functional response of fish. Therefore, the results suggest that aggregating may be maladaptive as an anti-vertebrate-predation defense in the case of zooplankton.