Small is Powerful: Demonstration of the Impact of Nanoformed Piroxicam in a Controlled Clinical Study.

PURPOSE: New solutions are needed to enable the efficient use of poorly water-soluble drugs. Therefore, we aimed to demonstrate that decreasing particle size with a solution-to-particle method known as nanoforming can improve dissolution and thus bioavailability. METHODS: Piroxicam, a poorly water-soluble non-steroidal anti-inflammatory drug (NSAID), was used as a model compound. A Quality-by-Design (QbD) approach was used to nanoform piroxicam and a design space was established. The pharmacokinetics of piroxicam nanoparticles were compared to two marketed products in a clinical trial. RESULTS: Nanoformed tablets showed a 33% increase in exposure during the first hour after dosing (AUC0-1 h) compared with an immediate release tablet and was similar to a fast absorbing tablet incorporating complexation of piroxicam with ß-cyclodextrin. CONCLUSIONS: The results show that nanoforming enabled more rapid absorption in comparison to a typical marketed tablet and indicate that nanoforming is an alternative to complex formulation such as cyclodextrins based products. The study outcomes support the potential of nanoforming for producing fast-acting dosage forms of poorly soluble drugs.

New Insights into Nanoplastics Ecotoxicology: Effects of Long-Term Polystyrene Nanoparticles Exposure on Folsomia candida.

Despite the growing concern over nanoplastics' (NPls) environmental impacts, their long-term effects on terrestrial organisms remain poorly understood. The main aim of this study was to assess how NPls exposure impacts both the parental (F1) and subsequent generations (F2 and F3) of the soil-dwelling species Folsomia candida. After a standard exposure (28 days), we conducted a multigenerational study along three generations (84 days), applying polystyrene nanoparticles (PS NPs; diameter of 44 nm) as representatives of NPls. Endpoints from biochemical to individual levels were assessed. The standard test: PS NPs (0.015 to 900 mg/kg) had no effect in F. candida survival or reproduction. The multigenerational test: PS NPs (1.5 and 300 mg/kg) induced no effects on F. candida survival and reproduction along the three generations (F1 to F3). PS NPs induced no effects in catalase, glutathione reductase, glutathione S-transferases, and acetylcholinesterase activities for the juveniles of the F1 to F3. Oxidative damage through lipid peroxidation was detected in the offspring of F1 but not in the juveniles of F2 and F3. Our findings underscore the importance of evaluating multigenerational effects to gain comprehensive insights into the contaminants long-term impact, particularly when organisms are continuously exposed, as is the case with NPls.

Photoprotective bioactivity present in a unique marine bacteria collection from Portuguese deep sea hydrothermal vents.

Interesting biological activities have been found for numerous marine compounds. In fact, screening of phylogenetically diverse marine microorganisms from extreme environments revealed to be a rational approach for the discovery of novel molecules with relevant bioactivities for industries such as pharmaceutical and cosmeceutical. Nevertheless, marine sources deliverables are still far from the expectations and new extreme sources of microbes should be explored. In this work, a marine prokaryotic collection from four Mid-Atlantic Ridge (MAR) deep sea hydrothermal vents near the Azores Islands, Portugal, was created, characterized and tested for its photoprotective capacity. Within 246 isolates, a polyphasic approach, using chemotaxonomic and molecular typing methods, identified 23-related clusters of phenetically similar isolates with high indexes of diversity. Interestingly, 16S rRNA gene sequencing suggested the presence of 43% new prokaryotic species. A sub-set of 139 isolates of the prokaryotic collection was selected for biotechnological exploitation with 484 bacterial extracts prepared in a sustainable upscalling manner. 22% of the extracts showed an industrially relevant photoprotective activity, with two extracts, belonging to new strains of the species Shewanella algae and Vibrio fluvialis, uniquely showing UV-A, UV-B and UV-C protective capacity. This clearly demonstrates the high potential of the bacteria MAR vents collection in natural product synthesis with market applications.

A powerful yeast-based screening assay for the identification of inhibitors of indoleamine 2,3-dioxygenase.

Activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) underlies the course of several human pathological conditions and, to date, no efficacious therapeutic IDO inhibitors are available. We proposed to develop a robust screening system based on the use of yeast cells to identify new lead compounds for the pharmacological inhibition of IDO-the BLOCKADE platform. Yeast combines the advantages of a relevant surrogate model for eukaryotic cell processes with the amenity to miniaturization and automation. We brought added value to the system by increasing the stringency of our assay, as the BLOCKADE strain was not deleted for any efflux pump, thus creating additional challenges for test compounds to be identified as hits. Screening of a library of 50 080 small molecules led to the identification of 101 potential IDO inhibitors, a low hit rate of 0.2%, reflecting the stringent assay conditions imposed. Most important, secondary pharmacology assays in mammalian cells confirmed activity for 76% of the hits, whereas hepatotoxicity testing indicated that 87% of them displayed a safe profile. The high predictivity rates obtained using the BLOCKADE platform clearly validate our system as a powerful tool for drug discovery.