Designing an effective dissolution test for bilayer tablets tailored for optimal melatonin release in sleep disorder management.

This project aims to investigate the release performance of bilayer tablet (BL-Tablet) designed with both fast and slow-release technology, targeting sleep disorders. The tablet incorporates Melatonin, extracts of Eschscholzia californica and Melissa officinalis. In order to validate the effectiveness of the extended-release profile, an advanced dissolution test was herein proposed. This new method utilizes biorelevant intestinal fluid media and incorporates a stomach-to-intestine fluid changing (SIFC) system. To demonstrate the advantages of employing this method for assessing the controlled release profile of active ingredients, the dissolution results were compared with those obtained using the conventional EU Pharmacopoeia approach. Furthermore, the comparative analysis was extended to include a monolayer tablet version (ML-Tablet) lacking the slow-release technology. Technological characterization and bioaccessibility studies, including intestinal permeability test, were conducted as well to assess the pharmacological performance and bioavailability of active ingredients. The dissolution data recovered revealed that the two dissolution methods did not exhibit any significant differences in the release of ML-Tablet's. However, the dissolution profile of the BL-Tablet exhibited notable differences between the two methods particularly when assessing the behavior of the slow-release layer. In this scenario, both methods initially exhibited a similar release pattern within the first approximately 0.5 h, driven by the fast-release layer of the tablet. Following this, distinct gradual and sustained releases were observed, spanning 2.5 h for the EU Pharmacopoeia method and 8 h for the new SIFC-biorelevant dissolution method, respectively. Overall, the novel method demonstrated a substantial improvement compared to conventional EU Pharmacopoeia test in evaluating the performance of a controlled slow-release technology. Remarkably, the prolonged release technology did not have an adverse impact on melatonin intestinal absorption, and, consequently, maintaining its potential bioavailability of around 78%. Concluding, this research provides valuable insights into how the innovative dissolution test can assist formulators in developing controlled release formulations.

Psychometric properties of the Parkinson's disease Questionnaire-39 and its short form Parkinson's disease Questionnaire-8: A systematic review and meta-analysis.

Parkinson's disease (PD) affects Quality of Life (QoL), since it is responsible for cognitive impairment, non-motor, and motor symptoms. Outcome measures are fundamental for evaluating treatment's effect on QoL over time. This systematic review aimed to identify the psychometric properties of PDQ-39 and PDQ-8 in the different populations in which they were validated. The electronic databases systematically searched are MEDLINE (via PubMed), CINAHL, SCOPUS, and Web of Science; the research was conducted in July 2023. The psychometric properties considered were those of the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. Risk of bias was assessed using the COSMIN checklist. The search identified 1306 articles. 398 duplicates were eliminated; 908 articles were analyzed reading title and abstract; 799 were finally excluded because used PDQ-39 and PDQ-8 as outcome measures or were not dealing with psychometric properties; 66 articles were excluded after reading the full text. 43 articles were included in the review; meta-analysis showed all the Cronbach's alpha values were statistically significant for all the subscales of PDQ-39 and PDQ-8. PDQ-39 demonstrated to be a specific HRQoL questionnaire that is correlated with generic HRQoL questionnaires, in fact in many studies included in the review, correlations with SF-36 were found. In the last studies about psychometric properties of PDQ-8 emerged that it is a practical and informative instrument that can be easily used in clinical settings, especially in busy ones, but also in large-scale studies in which a brief instrument would be preferred.

Carbon dots for cancer nanomedicine: a bright future.

Cancer remains one of the main causes of death in the world. Early diagnosis and effective cancer therapies are required to treat this pathology. Traditional therapeutic approaches are limited by lack of specificity and systemic toxicity. In this scenario, nanomaterials could overcome many limitations of conventional approaches by reducing side effects, increasing tumor accumulation and improving the efficacy of drugs. In the past few decades, carbon nanomaterials (i.e., fullerenes, carbon nanotubes, and carbon dots) have attracted significant attention of researchers in various scientific fields including biomedicine due to their unique physical/chemical properties and biological compatibility and are among the most promising materials that have already changed and will keep changing human life. Recently, because of their functionalization and stability, carbon nanomaterials have been explored as a novel tool for the delivery of therapeutic cancer drugs. In this review, we present an overview of the development of carbon dot nanomaterials in the nanomedicine field by focusing on their synthesis, and structural and optical properties as well as their imaging, therapy and cargo delivery applications.

Organic Polyradicals as Redox Mediators: Effect of Intramolecular Radical Interactions on Their Efficiency.

The spin-spin interactions between unpaired electrons in organic (poly)radicals, especially nitroxides, are largely investigated and are of crucial importance for their applications in areas such as organic magnetism, molecular charge transfer, or multiple spin labeling in structural biology. Recently, 2,2,6,6-tetramethylpiperidinyloxyl and polymers functionalized with nitroxides have been described as successful redox mediators in several electrochemical applications; however, the study of spin-spin interaction effect in such an area is absent. This communication reports the preparation of a novel family of discrete polynitroxide molecules, with the same number of radical units but different arrangements to study the effect of intramolecular spin-spin interactions on their electrochemical potential and their use as oxidation redox mediators in a Li-oxygen battery. We find that the intensity of interactions, as measured by the d1/d electron paramagnetic resonance parameter, progressively lowers the reduction potential. This allows us to tune the charging potential of the battery, optimizing its energy efficiency.

Precursor-Dependent Photocatalytic Activity of Carbon Dots.

This work systematically compares both structural features and photocatalytic performance of a series of graphitic and amorphous carbon dots (CDs) prepared in a bottom-up manner from fructose, glucose, and citric acid. We demonstrate that the carbon source and synthetic procedures diversely affect the structural and optical properties of the CDs, which in turn unpredictably influence their photo electron transfer ability. The latter was evaluated by studying the photo-reduction of methyl viologen. Overall, citric acid-CDs were found to provide the best photocatalytic performance followed by fructose- and glucose-CDs. However, while the graphitization of glucose- and citric acid-CDs favored the photo-reaction, a reverse structure-activity dependence was observed for fructose-CDs due to the formation of a large graphitic-like supramolecular assembly. This study highlights the complexity to design in advance photo-active bio-based carbon nanomaterials.

Design of Carbon Dots for Metal-free Photoredox Catalysis.

The photoreduction potential of a set of four different carbon dots (CDs) was investigated. The CDs were synthesized by using two different preparation methods-hydrothermal and pyrolytic-and two sets of reagents-neat citric acid and citric acid doped with diethylenetriamine. The hydrothermal syntheses yielded amorphous CDs, which were either nondoped (a-CDs) or nitrogen-doped (a-N-CDs), whereas the pyrolytic treatment afforded graphitic CDs, either non-doped (g-CDs) or nitrogen-doped (g-N-CDs). The morphology, structure, and optical properties of four different types of CDs revealed significant differences depending on the synthetic pathway. The photocatalytic activities of the CDs were investigated as such, that is, in the absence of any other redox mediators, on the model photoreduction reaction of methyl viologen. The observed photocatalytic reaction rates: a-N-CDs ≥ g-CDs > a-CDs ≥ g-N-CDs were correlated with the presence/absence of fluorophores, to the graphitic core, and to quenching interactions between the two. The results indicate that nitrogen doping reverses the photoredox reactivity between amorphous and graphitic CDs and that amorphous N-doped CDs are the most photoredox active, a yet unknown fact that demonstrates the tunable potential of CDs for ad hoc applications.

Carbon Dots from Sugars and Ascorbic Acid: Role of the Precursors on Morphology, Properties, Toxicity, and Drug Uptake.

There is the need for reproducible, simple, high-yielding synthetic protocols aimed at obtaining carbon dots (CDs) with controlled fluorescence, photothermal and photochemical behavior, surface properties, biocompatibility, tumor targeting ability, drug absorption biodistribution, and tumor uptake. This Letter describes a systematic study on the effect of glucose, fructose, and ascorbic acid as starting materials for the preparation of highly luminescent CDs, characterized by a blue emission. Their composition and morphology are investigated by titration of OH surface groups, spectroscopic techniques, and high-resolution transmission electron microscopy (HR-TEM), and their toxicity was tested toward HeLa cells. CDs made using fructose were toxic, while those made from glucose and ascorbic acid showed good biocompatibility. The reproducible and simple synthetic procedure yields luminescent biomass-derived CDs for combined cancer therapy and diagnostics. Their doxorubicin (DOX) drug uptake was measured by spectrofluorimetry, indicating a crucial role of the morphologies of the CDs in controlling DOX loading. The glucose derived CDs showed up to 28% w/w of DOX loading.

Catalytic properties of [Pd(COOMe)(n)X(2-n)(PPh(3))(2)] (n = 0, 1, 2; X = Cl, NO(2), ONO(2), OAc and OTs) in the oxidative carbonylation of MeOH.

cis-[Pd(ONO(2))(2)(PPh(3))(2)] (1) reacts under mild conditions with CO in methanol (MeOH) in the presence of pyridine (py), yielding trans-[Pd(COOMe)(ONO(2))(PPh(3))(2)] (1a). The use of NEt(3) instead of py leads to a mixture of 1a, trans-[Pd(COOMe)(2)(PPh(3))(2)] (2), and [Pd(CO)(PPh(3))(3)]. Pure 2 was prepared by reacting cis-[Pd(OTs)(2)(PPh(3))(2)] with CO in MeOH and subsequently adding NEt(3). The nitro complex trans-[Pd(COOMe)(NO(2))(PPh(3))(2)] (3a) was prepared by reacting trans-[Pd(COOMe)Cl(PPh(3))(2)] with AgNO(2) or with AgOTs and NaNO(2). New syntheses for 1 and trans-[Pd(NO(2))(2)(PPh(3))(2)] (3) are also reported. All complexes have been characterized by IR and (1)H and (31)P{(1)H} NMR spectroscopies. Complexes 1 and 2 exchange irreversibly and quantitatively one nitrato with one carbomethoxy ligand, yielding 1a. 2 in CD(2)Cl(2) at 40 degrees C decomposes with the formation of dimethyl carbonate (DMC), whereas under 4 atm of CO, DMC and dimethyl oxalate (DMO) are formed, ca. 12% each; in the presence of PPh(3) and in the absence of CO, decomposition occurs at 60 degrees C with the formation of DMC only, suggesting that decarbonylation involves a five-coordinate intermediate or predissociation of a PPh(3) ligand. The oxidative carbonylation of MeOH does not occur when using NaNO(2) or NaNO(3) as the oxidant and 1, 1a, 3, or 3a as the catalyst precursor. On the contrary, when using benzoquinone (BQ) as the oxidant, these complexes, 2, or [Pd(COOMe)(2-n)X(n)(PPh(3))(2)] (X = Cl, OAc, OTs; n = 1, 2) promote selective catalysis to DMO. After catalysis the precursors are transformed into [Pd(BQ)(PPh(3))(2)](2).H(2)BQ, [Pd(CO)(PPh(3))](3) and [Pd(CO)(PPh(3))(3)]. Also the last with BQ gives selective catalysis to DMO. The solid-state structures of 1.CH(2)Cl(2) and 1a have been determined by means of single-crystal X-ray diffraction.