Buccal Thin Films as Potent Permeation Enhancers for Cytisine Transbuccal Delivery

Cytisine (CYT) is a powerful anti-smoking compound which could greatly benefit from transbuccal delivery because of both its unfavorable pharmacokinetics after oral administration and its intrinsic ability to permeate the buccal mucosa. This work aims to design CYT-loaded buccal thin films suitable for transbuccal drug delivery due to its capability of promoting the interaction between CYT and the buccal membrane. The solvent casting method was employed to prepare several thin films combining various excipients such as matrixing polymers, mucoadhesion agents, plasticizers and other compounds as humectants and sweeteners, component ratios and solvents. A total of 36 compositions was prepared and four of them emerged as the most promising in terms of aspect and flexibility. They all demonstrated homogeneity, thinness, low swelling degree, and controlled drug release according to the Power Law and Peppas-Sahlin mathematical models. Mainly, they proved able to interact with the ex vivo porcine buccal mucosa producing mucoadhesive effects, and act as potent permeation enhancers. In particular, Film B emerged as suitable as it produced a 10.6-fold Kp enhancement and a great Js value (52.33 μg/cm2·h-1), even when compared to highly concentrated CYT solutions

Green next generation biomaterials from virtuous recovery of grape processing waste bentonite

The waste valorisation, by conversion of discharge products into novel high value-added biomaterials, represents a virtuous strategy to contribute to the ecological transition while producing social, economic and scientific repercussions. Even more, the recycle of wastes from the local resources could maximize the impact of the circular economy idea by enhancing the territorial resources and creating new products free from additional raw materials consumption. About this, the grape processing industry is an undoubted Sicilian prestige, but it also produces abundant both organic and inorganic wastes. While grape pomace has been extensively valorised in the last years, the inorganic wastes have never been considered yet. The latter are mainly the fining agents, among which bentonite is the most common one. It is a mineral clay widely used due to low cost, abundance in nature, high clarifying power and ease of separation from the fined product by sedimentation. So far, the bentonite is just an abundant waste (100g of bentonite to fine 1hL of must/wine) then the aim of this work is to recognize it as a precious source of polyphenols to be given new life by extraction. The frozen waste black bentonite was supplied by Bono&Ditta S.p.A. Once arrived at the University of Palermo it was subjected to pulverization, sieved, divided into aliquots identified as belonging to the same lot and stored at -80°C. Samples of bentonite were subjected to green extraction by maceration (1h, 25°C, constant stirring, in the dark) choosing unconventional extraction solvents among well-known and currently used hydrophilic liquid excipients for pharmaceuticals and cosmetics. They were PEGs (PEG200, PEG400, PEG600), propylene glycol and glycerine, selected due to their high solvent power toward polyphenols and biocompatibility. The coloured liquid extracts were characterized and compared in terms of antioxidant power/scavenging activity by DPPH assay, chromatographic profile and extracted amount of some representative polyphenols by HPLC-DAD analyses, total phenolic and protein contents by Folin-Ciocalteu and Bradford assays respectively. The best extract was obtained by using PEG200 and was then further studied. It resulted stable at easily achievable storage conditions (4°C, in the dark) for at least 6 months. Furthermore, it is suitable as a novel, value-added biomaterial for biomedical and cosmetic purposes as nor skin/eye irritation neither skin sensitising potential emerged by the in vitro tests, according to OECD 439/492/442E guidelines. Importantly, the “green soul” of this work is not just related to waste bentonite valorisation. The extraction procedure can be considered eco-friendly both in terms of employed technique and chosen extraction solvents. This choice perfectly fit with an industrial, easily scalable and waste-to-market approach as well as with the SDGs 12, 8 and 3 of the UN agenda 2030

A molecular beacon, bead-based assay for the detection of nucleic acids by flow cytometry

Molecular beacons are dual-labelled probes that are typically used in real-time PCR assays, but have also been conjugated with solid matrices for use in microarrays or biosensors. We have developed a fluid array system using microsphere-conjugated molecular beacons and the flow cytometer for the specific, multiplexed detection of unlabelled nucleic acids in solution. For this array system, molecular beacons were conjugated with microspheres using a biotin-streptavidin linkage. A bridged conjugation method using streptavidin increased the signal-to-noise ratio, allowing for further discrimination of target quantitation. Using beads of different sizes and molecular beacons in two fluorophore colours, synthetic nucleic acid control sequences were specifically detected for three respiratory pathogens, including the SARS coronavirus in proof-of-concept experiments. Considering that routine flow cytometers are able to detect up to four fluorescent channels, this novel assay may allow for the specific multiplex detection of a nucleic acid panel in a single tube

Viral hemorrhagic fevers: advancing the level of treatment

The management of viral hemorrhagic fevers (VHFs) has mainly focused on strict infection control measures, while standard clinical interventions that are provided to patients with other life-threatening conditions are rarely offered to patients with VHFs. Despite its complexity, a proper clinical case management of VHFs is neither futile nor is it lacking in scientific rationale. Given that patient outcomes improve when treatment is started as soon as possible, development and implementation of protocols to promptly identify and treat patients in the earliest phases of diseases are urgently needed. Different pharmacological options have been proposed to manage patients and, as for other life-threatening conditions, advanced life support has been proved effective to address multiorgan failure. In addition, high throughput screening of small molecular libraries has emerged as a novel promising way to find new candidates drugs for VHFs therapy and a relevant number of new molecules are currently under investigation. Here we discuss the current knowledge about VHF clinical management to propose a way to step up the approach to VHFs beyond the mere application of infection control measures

New experimental test of Bell inequalities by the use of a non-maximally entangled photon state

We report on the first realisation of a test of Bell inequalities using non-maximally entangled states. It is based on the superposition of type I parametric down conversion produced in two different non-linear crystals pumped by the same laser, but with different polarisations. We discuss the advantages and the possible developments of this configuration.Comment: accepted for publicatio

Lipid Nanoparticles Loaded With Resveratrol And Glycyrrhetinic Acid As New Tool For Wound Healing

Skin and mucous membranes maintain the homeostasis of the full body and are the first barriers against microbial infections. Therefore, their integrity is crucial and any lesion or injury must be quickly treated. In healthy people, several steps, such as inflammation, production of pro-oxidative species, cells proliferation and remodelling, follow each other creating a cascade process that determine the total restoration of the injured tissue. However, even a single discrepancy in these phases can delay the wound healing or irreversibly compromise the tissue. A smart strategy to promote wound healing could be the administration of natural compounds such as polyphenols and triterpenoids which are characterized by strong antioxidant and anti-inflammatory activities, antimicrobial properties and low side effects. However, the beneficial effects of these molecules are limited by their disadvantageous physico-chemical properties (e.g., low solubility in water, degradation) that compromise their bioavailability and thereby their clinical use. Based on these considerations, the aim of this work was to prepare and characterize a novel drug delivery system in form of multicomponent lipid nanoparticles (LNPs) constituted by a complex mixture of PEGylated lipid, Glyceryl monoester and Menthol able to entrap the polyphenol Resveratrol (RSV) and the triterpenoid Glycyrrhetinic Acid (GA) in order to protect them from degradation and maximize their effectiveness so as to make them useful for the wound management. Following optimization of the lipid blend composition and excipient ratios, it resulted homogeneous, with a melting range temperature of 57-61°C and containing GA (2.73 ± 0.23%w/w) and RSV (4.56 ± 0.04%w/w) in the amorphous form. The LNPs, obtained by homogenization followed by high-frequency sonication, were characterized by DLS and SEM analyses resulting almost monodispersed (PDI: 0.267 ± 0.010), with spherical shape (by SEM), nanometric size (162.86 ± 3.12nm) and suitable Z-potential (-21.40 ± 7.33mV). The quantitative analyses showed high encapsulation efficiency for both RSV and GA having a suitable DR% (96.82 ± 1.34% and 99.6 ± 1.29%, respectively) and LE% (96.82 ± 1.34% and 97.15 ± 0.19%, respectively) values. RSV release studies highlighted a sustained and controlled pattern of discharge to different chemical environments simulating the wound conditions. Moreover, LNPs showed significant scavenger properties evaluated by the DPPH assay. Last, the biological evaluations (scratch assay) highlighted an enhanced fibroblasts proliferation and migration at extremely low doses (LNPs 22 μg/mL corresponding to RSV 5 μM). Furthermore, a promising antibiofilm effect against Staphilococcus aureus was observed in a dose-dependent manner. In conclusion, these novel multicomponent LNPs could represent a next generation carrier constituting a promising tool for wound healing purposes

Orthopoxvirus Seroprevalence in Cats and Veterinary Personnel in North-Eastern Italy in 2011

Orthopoxviruses (OPV) are emerging zoonotic pathogens, and an increasing number of human infections is currently reported in Europe and in other continents, warranting heightened attention on this topic. Following two OPV infections reported in veterinarians scratched by sick cats in 2005 and 2007 in North-Eastern-Italy, involving a previously undescribed OPV, a similar strain was isolated by a sick cat from the same territory in 2011, i.e., 6 years later, raising attention on OPV circulation in this region. A surveillance program was launched to assess the OPV seroprevalence among the veterinarians working in local veterinary clinics and in the local wild and domestic cat population; seroprevalence was 33.3% in veterinarians and 19.5% in cats. Seroprevalence in cats was unevenly distributed, peaking at 40% in the area where OPV-infected cats had been observed

Multicomponent Antibiofilm Lipid Nanoparticles as Novel Platform to Ameliorate Resveratrol Properties: Preliminary Outcomes on Fibroblast Proliferation and Migration

: The well-being of skin and mucous membranes is fundamental for the homeostasis of the body and thus it is imperative to treat any lesion quickly and correctly. In this view, polyphenols might assist and enhance a successful wound healing process by reducing the inflammatory cascade and the production of free radicals. However, they suffer from disadvantageous physico-chemical properties, leading to restricted clinical use. In this work, a complex mixture of PEGylated lipid, Glyceryl monoester, 18-β-Glycyrrhetinic Acid and Menthol was designed to entrap Resveratrol (RSV) as the active ingredient and further produce lipid nanoparticles (LNPs) by homogenization followed by high-frequency sonication. The nanosystem was properly characterized in terms of particle size (DLS, SEM), zeta potential, drug loading, antioxidant power (DPPH), release behaviour, cytocompatibility, wound healing and antibiofilm properties. The optimized lipid mixture was homogeneous, melted at 57-61 °C and encapsulated amorphous RSV (4.56 ± 0.04% w/w). The RSV-loaded LNPs were almost monodispersed (PDI: 0.267 ± 0.010), with nanometric size (162.86 ± 3.12 nm), scavenger properties and suitable DR% and LE% values (96.82 ± 1.34% and 95.17 ± 0.25%, respectively). The release studies were performed to simulate the wound conditions: 1-octanol to mimic the lipophilic domains of biological tissues (where the First Order kinetic was observed) and citrate buffer pH 5.5 according to the inflammatory wound exudate (where the Korsmeyer-Peppas kinetic was followed). The biological and microbiological evaluations highlighted fibroblast proliferation and migration effects as well as antibiofilm properties at extremely low doses (LNPs: 22 μg/mL, corresponding to RSV 5 µM). Thus, the proposed multicomponent LNPs could represent a valuable RSV delivery platform for wound healing purposes

About entanglement properties of kaons and tests of hidden variables models

In this letter we discuss entanglement properties of neutral kaons systems and their use for testing local realism. In particular we show that, as previous proposals, also a scheme recently suggested for performing a test of hidden variable theories against standard quantum mechanics cannot be conclusive