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NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94-98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain.The emerging pathogen Candida aurisis an emerging fungal pathogen that was associated with nosocomial infectious outbreaks. Its worldwide incidence and the emerging multidrug-resistant strains highlight the urgency for novel and effective antifungal treatment strategies. Lippia sidoides essential oil (LSEO) proved antifungal activity, including anti-Candida. However, it may undergo irreversible changes when in contact with external agents without adequate protection. Herein, we encapsulated LSEO in nanostructured lipid carriers (NLC) through the hot emulsification method followed by sonication. NLC matrix was based on oleic acid and Compritol® 888, or a combination of carnauba wax and beeswax, stabilized by sodium dodecyl sulfate. Eight formulations were produced and characterized by the determination of the particle size (213.1 to 445.5 nm), polydispersity index (around 0.3), and ζ-potential (-93.1 to -63.8 mV). The antifungal activity of nanoparticles and LSEO against C. auris and the in vivo toxicity in Galleria mellonella model were also evaluated. Both NLC and LSEO exhibited potent activity against the yeast, with Minimum Inhibitory Concentration between 281 and 563 µg/mL, and did not evidence toxicity in the in vivo model. Therefore, this study confirms the viability of NLCs loaded with LSEO in combating drug-resistant pathogens as a potential new therapeutic strategy for managing of candidemia.The performance of solid oral dosage forms targeting the colon is typically evaluated using standardised pharmacopeial dissolution apparatuses. However, these fail to replicate colonic hydrodynamics. This study develops a digital twin of the Dynamic Colon Model; a physiologically representative in vitro model of the human proximal colon. Magnetic resonance imaging of the Dynamic Colon Model verified that the digital twin robustly replicated flow patterns under different physiological conditions (media viscosity, volume, and peristaltic wave speed). During local contractile activity, antegrade flows of 0.06-0.78 cm s-1 and backflows of -2.16--0.21 cm s-1 were measured. Mean wall shear rates were strongly time and viscosity dependent although peaks were measured between 3.05-10.12 s-1 and 5.11-20.34 s-1 in the Dynamic Colon Model and its digital twin respectively, comparable to previous estimates of the USPII with paddle speeds of 25 and 50 rpm. It is recommended that viscosity and shear rates are considered when designing future dissolution test methodologies for colon-targeted formulations. In the USPII, paddle speeds >50 rpm may not recreate physiologically relevant shear rates. These findings demonstrate how the combination of biorelevant in vitro and in silico models can provide new insights for dissolution testing beyond established pharmacopeial methods.During the development of a pharmaceutical formulation, a powerful tool is needed to extract the key points from the complicated process parameters and material attributes. Artificial neural networks (ANNs), a promising and more flexible modeling technique, can address real intricate questions in a high parallelism and distributed pattern in the manner of biological neural networks. The data mined and analyzing based on ANNs have the ability to replace hundreds of trial and error experiments. ANNs have been used for data analysis by pharmaceutics researchers since the 1990s and it has now become a research method in pharmaceutical science. This review focuses on the latest application progress of ANNs in the prediction, characterization and optimization of pharmaceutical formulation to provide a reference for the further interdisciplinary study of pharmaceutics and ANNs.The main aim of this work is the biopharmaceutical characterization of a new hybrid benzodiazepine-dihydropyridine derivative, JM-20, derived with potent anti-ischemic and neuroprotective effects. In this study, the pKa and the pH-solubility profile were experimentally determined. Additionally, effective intestinal permeability was measured using three in vitro epithelial cell lines (MDCK, MDCK-MDR1 and Caco-2) and an in situ closed-loop intestinal perfusion technique. The results indicate that JM-20 is more soluble at acidic pH (9.18 ± 0.16); however, the Dose number (Do) was greater than 1, suggesting that it is a low-solubility compound. The permeability values obtained with in vitro cell lines as well as with the in situ perfusion method show that JM-20 is a highly permeable compound (Caco-2 value 3.8 × 10-5). selleck chemicals llc The presence of an absorption carrier-mediated transport mechanism was also demonstrated, as well as the efflux effect of P-glycoprotein on the permeability values. Finally, JM-20 was provisionally classified as class 2 according to the biopharmaceutical classification system (BCS) due to its high intestinal permeability and low solubility. The potential good oral absorption of this compound could be limited by its solubility.Nanoparticles (NPs) are at the leading edge of nanomedicine, and determining their biosafety remains a mandatory precondition for biomedical applications. Herein, we explore the bioassimilation of copper sulfide NPs reported as powerful photo-responsive anticancer therapeutic agents. The nanoparticles investigated present a hollow shell morphology, that can be left empty (CuS NPs) or be filled with an iron oxide flower-like core (iron oxide@CuS NPs), and are compared with the iron oxide nanoparticles only (iron oxide NPs). CuS, iron oxide@CuS and iron oxide NPs were injected in 6-week-old mice, at doses coherent with an antitumoral treatment. Cu and Fe were quantified in the liver, spleen, kidneys, and lungs over 6 months, including the control animals, thus providing endogenous Cu and Fe levels in the first months after animal birth. After intravenous NPs administration, 77.0 ± 3.9% of the mass of Cu injected, and 78.6 ± 3.8% of the mass of Fe, were detected in the liver. In the spleen, we found 3.3 ± 0.6% of the injected Cu and 3.8 ± 0.6% for the Fe. No negative impact was observed on organ weight, nor on Cu or Fe homeostasis in the long term. The mass of the two metals returned to the control values within three months, a result that was confirmed by transmission electron microscopy and histology images. This bioassimilation with no negative impact comforts the possible translation of these nanomaterials into clinical practice.Mitochondria, organelles surrounded by a double membrane and with their own small genome, are the cells' energy centres [...].Tablet manufacturing involves the processing of raw materials through several unit operations. Thus, the mitigation of input-induced variability should also consider the downstream processability of intermediary products. The objective of the present work was to study the effect of variable raw materials and processing conditions on the compression properties of granules containing two active pharmaceutical ingredients (APIs) and microcrystalline cellulose. Differences in compressibility and tabletability of granules were highlighted in function of the initial particle size of the first API, granule polydispersity and fragmentation. Moreover, interactions were underlined with the atomizing pressure. Changing the supplier of the second API was efficiently controlled by adapting the binder addition rate and atomizing pressure during granulation, considering the starting crystal size. By fitting mathematical models on the available compression data, the influence of diluent source on granule compactibility and tabletability was identified. These differences resumed to the ease of compaction, tableting capacity and pressure sensitivity index due to variable water binding capacity of microcrystalline cellulose. Building the design space enabled the identification of suitable API types and the appropriate processing conditions (spray rate, atomizing pressure, compression force) required to ensure the desired tableting performance.The present study brings to attention a method to develop salicylic acid-based oil in water (O/W) microemulsions using a tensioactive system based on Tween 80, lecithin, and propylene glycol (PG), enriched with a vegetable oat oil phase and hyaluronic acid. The systems were physically characterized and the Quality by design approach was applied to optimize the attributes of microemulsions using Box-Behnken modeling, combined with response surface methodology. For this purpose, a 33 fractional factorial design was selected. The effect of independent variables namely X1 Tween 80/PG (%), X2 Lecithin (%), X3 Oil phase (%) was analyzed considering their impact upon the internal structure and evaluated parameters chosen as dependent factors viscosity, mean droplet size, and work of adhesion. A high viscosity, a low droplet size, an adequate wettability-with a reduced mechanical work-and clarity were considered as desirable for the optimal systems. It was found that the optimal microemulsion which complied with the established conditions was based on Tween 80/PG 40%, lecithin 0.3%, oat oil 2%, salicylic acid 0.5%, hyaluronic acid 1%, and water 56.2%. The response surface methodology was considered an appropriate tool to explain the impact of formulation factors on the physical properties of microemulsions, offering a complex pattern in the assessment of stability and quality attributes for the optimized formulation.Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PLpro), and 3C-like protease (3CLpro) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding domain (RBD) was considered an important factor in the present assessment. Finally, the antiviral potency of compounds was validated using a plaque reduction assay. Our funnel strategy revealed that tamoxifen possesses an anti-SARS-CoV-2 property owing to its inhibitory performance in multiple assays. The proposed time-saving and feasible strategy may accelerate drug screening for COVID-19 and other diseases.
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