An Integrated Study to Evaluate Debris Flow Hazard in Alpine Environment

Debris flows are among the most dangerous natural processes affecting the alpine environment due to their magnitude (volume of transported material) and the long runout. The presence of structures and infrastructures on alluvial fans can lead to severe problems in terms of interactions between debris flows and human activities. Risk mitigation in these areas requires identifying the magnitude, triggers, and propagation of debris flows. Here, we propose an integrated methodology to characterize these phenomena. The methodology consists of three complementary procedures. Firstly, we adopt a classification method based on the propensity of the catchment bedrocks to produce clayey-grained material. The classification allows us to identify the most likely rheology of the process. Secondly, we calculate a sediment connectivity index to estimate the topographic control on the possible coupling between the sediment source areas and the catchment channel network. This step allows for the assessment of the debris supply, which is most likely available for the channelized processes. Finally, with the data obtained in the previous steps, we modelled the propagation and depositional pattern of debris flows with a 3D code based on Cellular Automata. The results of the numerical runs allow us to identify the depositional patterns and the areas potentially involved in the flow processes. This integrated methodology is applied to a test-bed catchment located in Northwestern Alps. The results indicate that this approach can be regarded as a useful tool to estimate debris flow related potential hazard scenarios in an alpine environment in an expeditious way without possessing an exhaustive knowledge of the investigated catchment, including data on historical debris flow events

Cyclodextrin-Based Nanohydrogels Containing Polyamidoamine Units: A New Dexamethasone Delivery System for Inflammatory Diseases

Glucocorticoids are widely prescribed in treatment of rheumatoid arthritis, asthma, systemic lupus erythematosus, lymphoid neoplasia, skin and eye inflammations. However, well-documented adverse effects offset their therapeutic advantages. In this work, novel nano-hydrogels for the sustained delivery of dexamethasone were designed to increase both bioavailability and duration of the administered drug and reducing the therapeutic dose. Hydrogels are soft materials consisting of water-swollen cross-linked polymers to which the insertion of cyclodextrin (CD) moieties adds hydrophobic drug-complexing sites. Polyamidoamines (PAAs) are biocompatible and biodegradable polymers apt to create CD moieties in hydrogels. In this work, β or γ-CD/PAA nanogels have been developed. In vitro studies showed that a pretreatment for 24–48 h with dexamethasone-loaded, β-CD/PAA nanogel (nanodexa) inhibits adhesion of Jurkat cells to human umbilical vein endothelial cells (HUVEC) in conditions mimicking inflammation. This inhibitory effect was faster and higher than that displayed by free dexamethasone. Moreover, nanodexa inhibited COX-2 expression induced by PMA+A23187 in Jurkat cells after 24–48 h incubation in the 10−8–10−5 M concentration range, while dexamethasone was effective only at 10−5 M after 48 h treatment. Hence, the novel nanogel-dexamethasone formulation combines faster action with lower doses, suggesting the potential for being more manageable than the free drug, reducing its adverse side effects

Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape

Cutaneous melanoma is one of the most aggressive solid tumors, with a low survival for the metastatic stage. Currently, clinical melanoma treatments include surgery, chemotherapy, targeted therapy, immunotherapy and radiotherapy. Of note, innovative therapeutic regimens concern the administration of multitarget drugs in tandem, in order to improve therapeutic efficacy. However, also, if this drug combination is clinically relevant, the patient’s response is not yet optimal. In this scenario, nanotechnology-based delivery systems can play a crucial role in the clinical treatment of advanced melanoma. In fact, their nano-features enable targeted drug delivery at a cellular level by overcoming biological barriers. Various nanomedicines have been proposed for the treatment of cutaneous melanoma, and a relevant number of them are undergoing clinical trials. In Italy, researchers are focusing on the pharmaceutical development of nanoformulations for malignant melanoma therapy. The present review reports an overview of the main melanoma-addressed nanomedicines currently under study in Italy, alongside the state of the art of melanoma therapy. Moreover, the latest Italian advances concerning the pre-clinical evaluation of nanomedicines for melanoma are described