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Background: Previous studies employing polymeric micelles and molecular imaging for in vivo nanosystem characterization have led to the development of radionanoprobes (RNPs) designed for diagnosing and monitoring therapeutic interventions in preclinical oncology research, specifically within breast and colon cancer models. These models exhibit high GLUT1 expression on tumor cells and VEGFR expression on the tumor vasculature. We aimed to enhance the tumor-targeting specificity of these RNPs by functionalizing micelles with glucose and bevacizumab. The choice of 99m Tc to label the nanoprobes is based on its availability and that direct labeling method is a widespread strategy to prepare radiopharmaceuticals using cold reagents and a 99 Mo/ 99m Tc generator. Soluplus ® is an attractive polymer for synthesizing micelles that also allows their functionalization. With all the above, the objective of this work was to design, develop and characterize nanoprobes based on polymeric micelles and radiolabeled with 99m Tc for the characterization of biological processes associated to the diagnosis, prognosis and monitoring of animal models of breast and colon cancer in preclinical research using molecular images., Results: Four RNPs ([ 99m Tc]Tc-Soluplus ® , [ 99m Tc]Tc-Soluplus ® +TPGS, [ 99m Tc]Tc-Soluplus ® +glucose and [ 99m Tc]Tc-Soluplus ® +bevacizumab) were produced with high radiochemical purity (> 95% in all cases) and stability in murine serum for up to 3 h. The RNPs maintained the 100 nm size of the Soluplus ® polymeric micelles even when they were functionalized and labeled with 99m Tc. The image acquisition protocol enabled the visualization of tumor uptake in two cancer experimental models using the assigned RNPs. In vivo biological characterization showed signal-to-background ratios of 1.7 ± 0.03 for [ 99m Tc]Tc-Soluplus ® +TPGS, 1.8 ± 0.02 for [ 99m Tc]Tc-Soluplus ® , and 2.3 ± 0.02 for [ 99m Tc]Tc-Soluplus ® +glucose in the breast cancer model, and 1.8 ± 0.04 for [ 99m Tc]Tc-Soluplus ® and 3.7 ± 0.07 for [ 99m Tc]Tc-Soluplus ® +bevacizumab in the colon cancer model. Ex vivo biodistribution, showed that the uptake of the tumors, regardless of the model, is < 2% IA/g while the blood activity concentration is higher, suggesting that the enhanced permeability and retention effect (EPR) would be one of the mechanisms involved in imaging tumors in addition to the active targeting of RNPs., Conclusions: Soluplus ® -based polymeric micelles provide a promising nanotechnological platform for the development of RNPs. The functionalization with glucose and bevacizumab enhances tumor specificity enabling effective imaging and monitoring of cancer in animal models., (© 2024. The Author(s).)

Enrichment of staple foods with proteins can be a solution to tackle protein-energy malnutrition in the elderly. For instance, bread can be enriched with pea proteins that are cheap, sustainable and easily digestible. Non-conventional technologies, such as high pressure homogenization (HPH), can improve the digestibility of plant proteins. To characterize the health functionality of pea-enriched bread, a functional bread tailored to elderly consumers was developed by substituting 5% wheat flour with untreated or HPH-treated pea protein concentrate. Protein digestibility and colon fermentability were assessed by mimicking elderly in vitro gastrointestinal and gut microbiota conditions and compared with adult conditions. Bread reformulation with pea proteins affected physical and chemical properties and produced an increase in hardness, which is one of the key features for the acceptability of bread by the elderly. The highest hardness value was observed for pea protein bread, followed by HPH-treated pea protein bread and wheat bread. In vitro protein digestibility and fermentability were affected by reformulation and by physiological digestive conditions, with lower digestibility under elderly conditions compared to adult ones. The obtained results may contribute to a better understanding of food digestibility under different gastrointestinal conditions and its dependence on physiological and formulation factors, and ultimately would help to design age-tailored foods.

Background: Ursodeoxycholic acid (UDCA) is a therapeutic agent used for the treatment of cholestatic hepatobiliary diseases in pediatric patients. It is a bile acid that presents high lipophilicity, and it belongs to Class II of the Biopharmaceutical Classification System (BCS), which exhibits low water solubility and high intestinal permeability, which leads to poor oral absorption. The objective of this work was to design and optimize UDCA nanosuspensions by means of the precipitation-ultrasonication method to improve the solubility, dissolution, and oral bioavailability of UDCA., Methods: A three-level, three-factor Box-Behnken design was used to optimize formulation variables and obtain uniform, small-particle-size UDCA nanosuspensions. The independent variables were: stabilizer percentage ( X 1 ), amplitude ( X 2 ), and sonication time ( X 3 ), and the dependent variable was the particle size ( Y 1 ). In the precipitation-ultrasonication method, UDCA was dissolved in acetone:PEG 400 (1:1 v / v ) and quickly incorporated into the antisolvent (pre-cooled aqueous dispersion of HPMC E-15 0.3%), by means of intense sonication at 50 W for 5 min, controlling temperature through an ice water bath. The lyophilization efficacy was evaluated by means of a cryoprotective efficacy test, working with 10% maltose at -80 °C. The nanosuspensions were characterized by dynamic light scattering (DLS), X-ray diffraction, and scanning electron microscopy (SEM). The physicochemical stability was determined at 25 °C and 4 °C at 7, 14, 30, and 60 days, and the UDCA content was analyzed via HPLC-UV. An in vitro dissolution assay and an oral bioavailability study were performed in male Wistar rats., Results: A significant impact was achieved in the optimized nanosuspension with 0.3% (stabilizer), 50 W (amplitude), and 5 min (sonication time), with a particle size of 352.4 nm, PDI of 0.11, and zeta potential of -4.30 mV. It presented adequate physicochemical stability throughout the study and the UDCA content was between 90% and 110%. In total, 86% of UDCA was dissolved in the in vitro dissolution test. The relative oral bioavailability was similar without significant statistical differences when comparing the lyophilized nanosuspension and the commercial tablet, the latter presenting a more erratic behavior. The pharmacokinetic parameters of the nanosuspension and the commercial tablet were T max (1.0 ± 0.9 h vs. 2.0 ± 0.8 h, respectively), C max (0.558 ± 0.118 vs. 0.366 ± 0.113 µM, respectively), ΔC max (0.309 ± 0.099 vs. 0.232 ± 0.056, respectively), AUC (4.326 ± 0.471 vs. 2.188 ± 0.353 µg/mL.h, respectively, p < 0.02), and IAUC 0-24h (2.261 ± 0.187 µg/mL.h vs. 1.924 ± 0.440 µg/mL.h, respectively)., Conclusions: The developed nanosuspension presents an appropriate dosage and administration for pediatric patients. On the other hand, it exhibits an adequate absorption and UDCA oral bioavailability.

In this study an in vitro static digestion method mimicking the elderly gastrointestinal conditions was designed by adapting the physiological parameters described in the INFOGEST standardized static in vitro digestion protocol, i.e., pH, digestive phase duration, concentrations of enzymes and bile salts, to the aged GI transit. The digestibility of proteins from different sources (pea, rice, wheat, and milk whey) was then assessed. Protein digestive behaviour was monitored after gastric and intestinal phases by BCA assay and SDS-PAGE to assess protein hydrolysis both from a quantitative and a qualitative point of view. Digested samples were also analysed for physical characteristics in terms of particle size and zeta potential. Data acquired under elderly gastrointestinal conditions were compared to those obtained by using the INFOGEST protocol designed to study adult digestion. Results clearly showed that the elderly gastrointestinal conditions deeply affected proteolysis leading to a general reduction of protein digestibility in comparison to the adult model. The proteolysis extent depended on the protein source with whey and rice proteins showing about 20% reduction using the model mimicking the elderly gut, followed by pea (about 10% reduction) and wheat (about 4% reduction) proteins. The knowledge of protein digestibility under elderly gastrointestinal conditions generated in this study could be useful in the attempt to develop age-tailored products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ageing is an unavoidable progressive process causing many changes of the individual life. However, if faced in an efficient way, living longer in a healthy status could be an opportunity for all. In this context, food consumption and dietary patterns are pivotal factors in promoting active and healthy ageing. The development of food products tailored for the specific needs of the elderly might favour the fulfilment of nutritionally balanced diets, while reducing the consequences of malnutrition. To this aim, the application of a food structure design approach could be particularly profitable, being food structure responsible to the final functionalities of food products. In this narrative review, the physiological changes associated to food consumption occurring during ageing were firstly discussed. Then, the focus shifted to the possible role of food structure in delivering target functionalities, considering food acceptability, digestion of the nutrients, bioactive molecules and probiotic bacteria.

Little is known about the oral processing behavior of gluten-free (GF) products. This study investigated the oral processing behavior of one commercial GF bread and one gluten-containing (GC) equivalent with and without spreads. Oral processing parameters were determined through video recording and the predominant texture attributes were accessed using a check-all-that-apply test. The GF bread was perceived crumbly, dry and sandy and had a longer eating duration than the GC bread, which was perceived soft, spongy, pasty and sticky. Results suggest that the structure of the GF bread was easily fragmented during mastication and a longer period in the mouth was required to prepare a cohesive bolus for swallowing. The addition of spreads increased softness perception but did not affect chewing behavior. Oral processing behavior of GF products should be further investigated to understand how eating rate, satiation responses and food intake can be modulated in GF products., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.

In recent years, the nanotechnology has offered researchers the opportunity to solve the problems caused by the vehicle of the standard and first formulation of paclitaxel (Taxol ® ), while maximizing the proven antineoplastic activity of the drug against many solid tumors. Hence, different types of nanocarriers have been employed to improve the efficacy, safety, physicochemical properties and pharmacokinetic/pharmacodynamic profile of this drug. To date, paclitaxel is the unique drug that is marketed in three different nanoplatforms for its parenteral delivery: polymeric nanoparticles (Abraxane ® ), liposomes (Lipusu ® ), and polymeric micelles (Genexol ® , Nanoxel ® and Paclical ® ). Indeed, a fourth nanocarrier might be available soon, because phase III studies of Opaxio™, a polymeric-conjugated, are near completion. Furthermore, other several nanoformulations are currently in various stages of clinical trials. Therefore, it is only through the critical analysis of clinical evidence from these studies that we can get a more concrete idea of what has been achieved with pharmaceutical nanotechnology so far. This review attempts to summarize current information available regarding the clinical status and the physicochemical characteristic of different nanocarriers for paclitaxel delivery in cancer therapy. We present an overview of the preclinical and clinical data of these systems including their pharmacokinetics, dose and administration, adverse events and clinical efficacy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Two clobazam aqueous suspensions for paediatric oral usage (5 mg/ml) were investigated to determinate its physicochemical stability under different storage conditions., Method: Formulations were stored at 4 and 25 °C and the clobazam content was determined by High Performance Liquid Chromatography. Each sample was analyzed by triplicate at different time points (0, 7, 14, 28 and 56 days)., Results: Liquid suspensions were successfully formulated from pure drug and commercially available tablets. In both cases, samples showed suitable physical stability. Clobazam was chemically stable in aqueous suspension during the 56 days of the study at the two storage temperatures., Conclusions: All the tried oral liquid formulations can be conserved at 4 and 25 °C at least 56-day period., (Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.)