π-Donor/π-Acceptor Interactions for the Encapsulation of Neurotransmitters on Functionalized Polysilicon-Based Microparticles.

Bipyridinium salts, commonly known as viologens, are π-acceptor molecules that strongly interact with π-donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of π-donor compounds such as catecholamines and indolamines. In this work, the synthesis and characterization of four gemini-type amphiphilic bipyridinium salts (1·4PF6-4·4PF6), and their immobilization either non-covalently or covalently on polysilicon surfaces and microparticles have been achieved. More importantly, they act as hosts for the subsequent incorporation of π-donor neurotransmitters such as dopamine, serotonin, adrenaline or noradrenaline. Ultraviolet-visible absorption and fluorescence spectroscopies and high-performance liquid chromatography were used to detect the formation of the complex in solution. The immobilization of bipyridinium salts and neurotransmitter incorporation on polysilicon surfaces was corroborated by contact angle measurements. The reduction in the bipyridinium moiety and the subsequent release of the neurotransmitter was achieved using ascorbic acid, or Vitamin C, as a triggering agent. Quantification of neurotransmitter encapsulated and released from the microparticles was performed using high-performance liquid chromatography. The cytotoxicity and genotoxicity studies of the bipyridinium salt 1·4PF6, which was selected for the non-covalent functionalization of the microparticles, demonstrated its low toxicity in the mouse fibroblast cell line (3T3/NIH), the human liver carcinoma cell line (HepG2) and the human epithelial colorectal adenocarcinoma cell line (Caco-2).

Three-tier testing approach for optimal ocular tolerance sunscreen.

Background: Poor ocular tolerance of sunscreens is partially responsible for poor compliance in use of sunscreens. A three-tiered approach for the testing of ocular tolerance for such products is described that includes an in vitro test for ocular irritation, an in vitro test for the activation of pain receptors, and finally a clinical study involving ocular instillation of the product under controlled conditions followed by ophthalmologic and subjective self-evaluation on a graded scale. We report the results for a new water-based facial sunscreen (SCFW) with very good ocular tolerance. Methods: The ocular irritation potential of SCFW was determined using the EpiOcular™ human cell construct which constituted the first-tier testing. Briefly, the tissues were exposed to SCFW and appropriate positive and negative controls for 15 minutes to 24 hours. After treatment, the tissues were rinsed and cytotoxicity determined. The calculated ET50 value (time at which relative viability decreased 50%) was then used to determine the ocular irritation potential. In the second-tier testing, the sting potential of SCFW was determined by employing the NociOcular assay that measures the activation of TRPV1 (transient receptor potential cation channel subfamily V member 1) specific receptors linked to pain sensation in a neuronal model with over-expression of functional TRPV1 channels. Finally, as the third-tier testing, SCFW was tested in a clinical study with instillation of product into the ocular cul-de-sac and ocular irritation was evaluated after 30 seconds, 15 minutes, and 60 minutes by an ophthalmologist. Participating subjects were also asked to score sensation on a scale of 0 to 3 from slight prickliness to severe stinging. Assay control reference product with known good ocular tolerability (10% baby shampoo) was concurrently tested. Results: In the in vitro topical application assay using the EpiOcular™ construct, no significant cytotoxicity was observed in the tissues exposed to SCFW, indicating minimal ocular irritation potential. In the in vitro NociOcular assay, the cells exposed to the prepared dilutions of SCFW showed minimal TRPV1 specific activity, indicating minimal ocular sting potential. In the in vivo study, no statistically significant differences were found in terms of subjective or objective eye irritation assessment between SCFW and 10% baby shampoo. Conclusion: SCFW showed negligible ocular irritation potential in tier 1, minimal potential to activate pain receptors in tier 2, and good ocular tolerability that was comparable to 10% baby shampoo in tier 3 testing. The results suggest that SCFW has good eye tolerance and that the tiered approach can be used to evaluate facial sunscreens for ocular tolerability.

Rhamnose-coated superparamagnetic iron-oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity.

Tumor recurrence after the incomplete removal of a tumor mass inside brain tissue is the main reason that scientists are working to identify new strategies in brain oncologic therapy. In particular, in the treatment of the most malignant astrocytic tumor glioblastoma, the use of magnetic nanoparticles seems to be one of the most promising keys in overcoming this problem, namely by means of magnetic fluid hyperthermia (MFH) treatment. However, the major unknown issue related to the use of nanoparticles is their toxicological behavior when they are in contact with biological tissues. In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron-oxide nanoparticles covalently coated with a rhamnose derivative, using proper cytotoxic assays. In the present study, we focused our attention on different strategies of toxicity evaluation comparing different cytotoxicological approaches in order to identify the biological damages induced by the nanoparticles. The data show an intensive internalization process of rhamnose-coated iron oxide nanoparticles by the cells, suggesting that rhamnose moiety is a promising biocompatible coating in favoring cells' uptake. With regards to cytotoxicity, a 35% cell death at a maximum concentration, mainly as a result of mitochondrial damages, was found. This cytotoxic behavior, along with the high uptake ability, could facilitate the use of these rhamnose-coated iron-oxide nanoparticles for future MFH therapeutic treatments.

In vitro safety toxicology data for evaluation of gold nanoparticles-chronic cytotoxicity, genotoxicity and uptake.

Safety and toxic effects of nanoparticles are still largely unexplored due to the multiple aspects that influence their behaviour toward biological systems. Here, we focus the attention on 12 nm spherical gold nanoparticle coated or not with hyaluronic acid compared to its precursor counterpart salt. Results ranging from the effects of a 10-days exposure in an in vitro model with BALB/c 3T3 fibroblast cells show how 12 nm spherical gold nanoparticles are internalized from 3T3 cells by endo-lysosomal pathway by an indirect measurement technique; and how gold nanoparticles, though not being a severe cytotoxicant, induce DNA damage probably through an indirect mechanism due to oxidative stress. While coating them with hyaluronic acid reduces gold nanoparticles cytotoxicity and slows their cell internalization. These results will be of great interest to medicine, since they indicate that gold nanoparticles (with or without coating) are suitable for therapeutic applications due to their tunable cell uptake and low toxicity.