Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product

Portal Venous Pressure as a Predictor of Mortality in Child’s A Cirrhotic Patients Undergoing Elective Surgery: A Prospective Study

BACKGROUND: Recently, portal venous pressure (PVP) exhibited high sensitivity and specificity in anticipating death in cirrhotic cases submitted to emergency operations. AIM: The current prospective work aimed to evaluate the utility of PVP in predicting 1st month post-operative death in Child’s A cirrhotic cases who underwent elective operations. METHODS: One-hundred and twenty cirrhotic cases that were planned to undergo elective surgery were enrolled in the current prospective work. The intraoperative (I.O) PVP and central venous pressure (CVP) were measured. The statistical analysis was performed using the SPSS version 22.0. The receiver operative curve was plotted to measure the predictive value of PVP. Multivariate analysis was done using logistic regression method for the significant variables impacting mortality on univariate analysis. RESULTS: Twenty-nine patients died in the current work. Patients who survived had statistically considerably lower PVP than patients who died (8.2 ± 1.5 vs. 12.5 ± 1.6 mmHg, respectively, p < 0.001). Similarly, patients who died had significantly higher I.O CVP (p < 0.001), body mass index (p < 0.001), and were more likely to have model for end-stage liver disease score between 9 and 16 (p = 0.003). At a cutoff value ≥10.5 mmHg, the PVP had a sensitivity of 82.8% and specificity of 93.4% for the prediction of mortality. The logistic regression analysis showed that only PVP (odds ratio [OR] =3.1, 95% confidence interval [CI] 1.25–7.5) and CVP (OR = 2.8, 95% CI 1.2–6.5) were the only independent predictors of mortality. CONCLUSION: PVP is a significant predictor of death in Child’s A cirrhotic cases submitted to elective operations

Targeted DPPC/DMPG surface-modified voriconazole lipid nanoparticles control invasive pulmonary aspergillosis in immunocompromised population: in-vitro and in-vivo assessment

Invasive pulmonary aspergillosis (IPA) is the most devastating Aspergillus-related lung disease. Voriconazole (VRZ) is the first-line treatment against IPA. Despite availability in oral and parenteral dosage forms, risks of systemic toxicity dictate alternative pulmonary administration. Inspired by natural lung surfactants, dipalmitoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DPPC/DMPG) surface-modified lipid nanoparticles (LNPs) were scrutinized for pulmonary administration. DPPC/DMPG-VRZ-LNPs prepared using ultrasonication/thin film hydration were investigated for colloidal properties over 3-month shelf storage. They were stable with a slight change in entrapment efficiency. They provided a sustained VRZ release over 24 h, with a rapid initial release. In vitro aerosolization indicated higher percentages of VRZ deposited on stages corresponding to secondary bronchi and alveolar ducts. Moreover, intrapulmonary administration maintained high lung VRZ concentration (27 ± 1.14 µg/g) after 6 h. A preclinical study using a cyclophosphamide-induced neutropenic rat model demonstrated a 3-fold reduction in BALF-Galactomannan down to 0.515 ± 0.22 µg/L confirming DPPC/DMPG-VRZ-LNPs potential in hyphal growth inhibition. Histopathological examination of infected/nontreated lung sections exhibited dense fungal load inside alveoli and blood vessels indicating massive tissue and angio-invasiveness. Nevertheless, DPPC/DMPG-VRZ-LNPs-treated animals displayed minimal hyphae with no signs of invasiveness. The developed bioinspired nanoparticles serve as prospective bioactive nanocarrier candidates for pulmonary administration of VRZ in the management of IPA

Protein Content and Oil Composition of Almond from Moroccan Seedlings: Genetic Diversity, Oil Quality and Geographical Origin

The protein and oil content and the fatty acid profile of the kernels of selected almond genotypes from four different Moroccan regions were determined in order to evaluate the kernel quality of the plant material of these different regions. The ranges of oil content (48.7–64.5 % of kernel DW), oleic (61.8–80.2 % of total oil), linoleic (11.4–27.0 %), palmitic (5.6–7.7 %), stearic (1.3–3.1 %), and palmitoleic (0.4–0.9 %) acid percentages agreed with previous results of other almond genotypes, but the protein content (14.1–35.1 % of kernel DW) showed that some genotypes had higher values than any previously recorded in almond. Some genotypes from mountainous regions showed kernels with very high oil content as well as high and consistent oleic and linoleic ratio, establishing a possible differentiation according to the geographical origin. These differences may allow establishing a geographical denomination for almond products. In terms of genetic diversity, oleic and linoleic acids were confirmed to be the most variable components of almond oil chemical composition among genotypes. Additionally, the genotypes with extreme favorable values, such as high protein content, could be incorporated into an almond breeding program aiming at an increase in kernel quality.Peer ReviewedPrunus amygdalusProtein contentOil contentFatty acidsQualityGenetic resourcesBreedingPublishe

Study of the material of the ATLAS inner detector for Run 2 of the LHC

Instituto de Física La Plat