Alendronate-Grafted Nanoemulsions for Bone-Targeted Vincristine Delivery: Preliminary Studies on Cell and Animal Models.

Bone is a site of distant metastases, which are a common cause of morbidity and mortality with a high socio-economic impact, for many malignant tumours. In order to engineer pharmacological therapies that are suitable for this debilitating disease, this experimental work presents injectable lipid nanoemulsions, which are endowed with a long history of safe clinical usage in parenteral nutrition, their loading with vincristine and their grafting with alendronate, with a dual purpose: merging the anticancer activity of bisphosphonates and vincristine, and enhancing bone-targeted delivery. In cell studies, alendronate synergised with the anti-migration activity of vincristine, which is important as migration plays a key role in the metastatisation process. In preliminary animal studies, carried out thanks to IVIS technology, alendronate conjugation enhanced the bone targeting of fluorescently labelled nanoemulsions. These encouraging results will drive further studies on suitable animal models of the disease.

Ultrasmall Solid-Lipid Nanoparticles via the Polysorbate Sorbitan Phase-Inversion Temperature Technique: A Promising Vehicle for Antioxidant Delivery into the Skin.

Solid lipid nanoparticles promote skin hydration via stratum corneum occlusion, which prevents water loss by evaporation, and via the reinforcement of the skin's lipid-film barrier, which occurs through the adhesion of the nanoparticles to the stratum corneum. The efficacy of both phenomena correlates with lower nanoparticle size and the increased skin permeation of loaded compounds. The so-called Polysorbate Sorbitan Phase-Inversion Temperature method has, therefore, been optimized in this experimental work, in order to engineer ultrasmall solid-lipid nanoparticles that were then loaded with α-tocopherol, as the anti-age ingredient for cosmetic application. Ultrasmall solid-lipid nanoparticles have been proven to be able to favor the skin absorption of loaded compounds via the aforementioned mechanisms.

Intranasal lipid nanocarriers: Uptake studies with fluorescently labeled formulations.

Drug delivery by the intranasal route allows both systemic absorption and non-invasive brain targeting, due to the unique connection provided by the olfactory and trigeminal nerves between the brain and the external environment. Lipid nanocarriers can improve intranasal drug delivery by enhancing bioadhesion to nasal mucosa, and by protecting the encapsulated drug from biological degradation and transport efflux proteins. In this study two different biocompatible lipid nanocarriers were compared: nanoemulsions and solid lipid nanoparticles. The nasal uptake was investigated by labeling the nanocarriers lipid matrix with two fluorescent probes, 6-coumarin and rhodamine B, both lipophilic, yet characterized by different water solubility, in order to mimic the behavior of hypothetic drug compounds. Ex vivo permeation, in vivo pharmacokinetics and biodistribution studies were performed. 6-coumarin, water insoluble and therefore integral with the lipid matrix, was taken up to a limited extent, within a long timeframe, but with a proportionally more pronounced brain accumulation. In nanoemulsions soluble rhodamine B showed a relevant systemic uptake, with good bioavailability, likely due to the prompt release of the probe at the nasal mucosa.

Nanosystems in Cosmetic Products: A Brief Overview of Functional, Market, Regulatory and Safety Concerns.

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.

mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation.

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.