Geant4 is a toolkit for simulating the passage of particles through matter. It includes a complete range of functionality including tracking, geometry, physics models and hits. The physics processes offered cover a comprehensive range, including electromagnetic, hadronic and optical processes, a large set of long-lived particles, materials and elements, over a wide energy range starting, in some cases, from View the MathML source and extending in others to the TeV energy range. It has been designed and constructed to expose the physics models utilised, to handle complex geometries, and to enable its easy adaptation for optimal use in different sets of applications. The toolkit is the result of a worldwide collaboration of physicists and software engineers. It has been created exploiting software engineering and object-oriented technology and implemented in the C++ programming language. It has been used in applications in particle physics, nuclear physics, accelerator design, space engineering and medical physics

Nanosystems exhibit various innovative physico-chemical properties as well as a range of cosmetic functions, including increased skin retention for loaded compounds. The worldwide nano-market has therefore been consistently extensive in recent decades. This review summarizes the most important properties of nanosystems that are employed in cosmetics, including composition, functions and interactions with skin, with particular attention being paid to marketed products. Moreover, the worldwide regulatory landscape of nanomaterials used as cosmetic ingredients is considered, and the main safety concerns are indicated. In general, advanced physico-chemical characterization is preliminarily needed to assess the safety of nanomaterials for human health and the environment. However, there is currently a shortfall in global legislation as a universally accepted and unambiguous definition of a nanomaterial is still lacking. Therefore, each country follows its own regulations. Anyhow, the main safety concerns arise from the European context, which is the most restrictive. Accordingly, the poor dermal permeation of nanomaterials generally limits their potential toxic effects, which should be mainly ascribed to unwanted or accidental exposure routes.

The anti-inflammatory cytokine Interleukin-10 (IL-10) is considered an efficient treatment for corneal inflammation, in spite of its short half-life and poor eye bioavailability. In the present work, mRNA-based nanomedicinal products based on solid lipid nanoparticles (SLNs) were developed in order to produce IL-10 to treat corneal inflammation. mRNA encoding green fluorescent protein (GFP) or human IL-10 was complexed with different SLNs and ligands. After, physicochemical characterization, transfection efficacy, intracellular disposition, cellular uptake and IL-10 expression of the nanosystems were evaluated in vitro in human corneal epithelial (HCE-2) cells. Energy-dependent mechanisms favoured HCE-2 transfection, whereas protein production was influenced by energy-independent uptake mechanisms. Nanovectors with a mean particle size between 94 and 348 nm and a positive superficial charge were formulated as eye drops containing 1% (w/v) of polyvinyl alcohol (PVA) with 7.1–7.5 pH. After three days of topical administration to mice, all formulations produced GFP in the corneal epithelium of mice. SLNs allowed the obtaining of a higher transfection efficiency than naked mRNA. All formulations produce IL-10, and the interleukin was even observed in the deeper layers of the epithelium of mice depending on the formulation. This work shows the potential application of mRNA-SLN-based nanosystems to address corneal inflammation by gene augmentation therapy.

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