scholarly journals Ex-Vivo and In-Vivo Assessment of Cyclamen europaeum Extract After Nasal Administration

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 426
Author(s):  
Fernández-Campos ◽  
Clares ◽  
Rodríguez-Lagunas ◽  
Jauregui ◽  
Casals ◽  
...  

Rhinosinusitis is a prevalent disorder with a severe impact on the health-related quality of life. Saponins of Cyclamen europaeum exert a clinically proven curative effect on rhinosinusitis symptoms when instilled into the nasal cavity, however, more extensive preclinical assessment is required to better characterize the efficacy of this botanical extract. This work evaluates the potential use of a natural freeze-dried extract of C. europaeum given as topical nasal administration. Permeation experiment on porcine nasal mucosa was performed with Franz diffusion cells. Experiments in rabbits were performed to test for any toxicological, hematological, biochemical or histological evidence of systemic action. No theoretical levels of saponins were found in the receptor chamber of Franz diffusion cells. Hematological data did not show significant differences between control and experimental animals (p > 0.05). Histological studies also showed that enhanced secretory activity in response to intranasal administration was not accompanied by any visible signs of injury. An examination of the brain, lungs, liver, kidneys, spleen, and gastrointestinal organs did not reveal any abnormality. The absence of mucosal permeation of saponins and negligible probability of C. europaeum saponins absorption in the course of a therapeutic application was demonstrated.

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Sarah E. Blutt ◽  
Mary K. Estes

Infectious diseases affect individual health and have widespread societal impacts. New ex vivo models are critical to understand pathogenesis, host response, and features necessary to develop preventive and therapeutic treatments. Pluripotent and tissue stem cell–derived organoids provide new tools for the study of human infections. Organoid models recapitulate many characteristics of in vivo disease and are providing new insights into human respiratory, gastrointestinal, and neuronal host–microbe interactions. Increasing culture complexity by adding the stroma, interorgan communication, and the microbiome will improve the use of organoids as models for infection. Organoid cultures provide a platform with the capability to improve human health related to infectious diseases. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 638 ◽  
Author(s):  
Aroha B. Sánchez ◽  
Ana C. Calpena ◽  
Mireia Mallandrich ◽  
Beatriz Clares

The absorption study of drugs through different biological membranes constitutes an essential step in the development of new pharmaceutical dosage forms. Concerning orally administered forms, methods based on monolayer cell culture of Caco-2 (Caucasian colon adenocarcinoma) have been developed to emulate intestinal mucosa in permeability studies. Although it is widely accepted, it has disadvantages, such as high costs or high technical complexity, and limitations related to the simplified structure of the monolayer or the class of molecules that can be permeated according to the transport mechanisms. The aim of this work was to develop a new ex vivo methodology which allows the evaluation of the intestinal apparent permeability coefficient (Papp) while using fewer resources and to assess the correlation with Caco-2. To this end, pig (Sus scrofa) duodenum segments were mounted in Franz diffusion cells and used to permeate four different drugs: ketorolac tromethamine (Kt), melatonin (Mel), hydrochlorothiazide (Htz), and furosemide (Fur). No statistically significant differences (p > 0.05) were observed corelating Papp values from Franz diffusion cells and Caco-2 cell experiments for Kt, Htz, and Fur. However, there were statistically significant differences (p < 0.05) correlating Papp values and Mel. The difference is explained by the role of Mel in the duodenal epithelial paracellular permeability reduction. Ex vivo permeation may be an equivalent method to Caco-2 for drugs that do not produce intestinal membrane phenomena that could affect absorption.


Drug Delivery ◽  
2009 ◽  
Vol 16 (3) ◽  
pp. 167-175 ◽  
Author(s):  
Cetin Tas ◽  
Cansel Kose Ozkan ◽  
Ayhan Savaser ◽  
Yalcin Ozkan ◽  
Umut Tasdemir ◽  
...  

Nanomedicine ◽  
2019 ◽  
Vol 14 (18) ◽  
pp. 2409-2422 ◽  
Author(s):  
Álvaro Casadomé-Perales ◽  
Laura De Matteis ◽  
Maria Alleva ◽  
Cristina Infantes-Rodríguez ◽  
Irene Palomares-Pérez ◽  
...  

Aim: To determine whether a p38 MAPK inhibitor incorporated into nanoemulsion-based chitosan nanocapsules can reduce the activity of this kinase in the brain through their nasal administration in mice. Materials & methods: We selected the p38 MAPK inhibitor PH797804, an ATP-competitive inhibitor of p38α encapsulated in nanoemulsion-based chitosan nanocapsules. Biological effect was evaluated in microglial and neuronal cells in vitro and in ex vivo and in vivo systems, in a mouse model of Alzheimer’s disease. Results: Encapsulated inhibitor retains enzymatic inhibitory activity and tissue penetration capacity in vitro, ex vivo and in vivo. Conclusion: Nasal administration of chitosan nanocapsules can be an effective approach for brain-restricted reduction of p38 MAPK activity, thus reducing the side effects of systemic administration.


2021 ◽  
Vol 11 (8) ◽  
pp. 3409
Author(s):  
Giulia Barzan ◽  
Alessio Sacco ◽  
Luisa Mandrile ◽  
Andrea Mario Giovannozzi ◽  
Chiara Portesi ◽  
...  

In this work, biomolecules, such as membrane proteins, lipids, and DNA, were identified and their spatial distribution was mapped within a single Escherichia coli cell by Raman hyperspectral imaging. Raman spectroscopy allows direct, nondestructive, rapid, and cost-effective analysis of biological samples, minimizing the sample preparation and without the need of chemical label or immunological staining. Firstly, a comparison between an air-dried and a freeze-dried cell was made, and the principal vibrational modes associated to the membrane and nucleic acids were identified by the bacterium’s Raman chemical fingerprint. Then, analyzing the Raman hyperspectral images by multivariate statistical analysis, the bacterium biological status was investigated at a subcellular level. Principal components analysis (PCA) was applied for dimensionality reduction of the spectral data, then spectral unmixing was performed by multivariate curve resolution–alternating least squares (MCR-ALS). Thanks to multivariate data analysis, the DNA segregation and the Z-ring formation of a replicating bacterial cell were detected at a sub-micrometer level, opening the way to real-time molecular analysis that could be easily applied on in vivo or ex vivo biological samples, avoiding long preparation and analysis process.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255015
Author(s):  
Laura López-Ríos ◽  
Miguel A. Barber ◽  
Julia Wiebe ◽  
Rubén P. Machín ◽  
Tanausú Vega-Morales ◽  
...  

Background This study was designed to evaluate the beneficial effects of a botanical extract combination containing soy isoflavone extract (100mg), Aframomum melegueta seed dry extract (50 mg), and Punica granatum skin dry extract (100mg) on health-related Quality of Life in healthy Spanish menopausal women with hot flashes, anxiety, and depressive symptoms using the validated Cervantes Scale. Methods and results Fifty-seven outpatient women (45–65 years) with menstrual problems associated with climacteric syndrome were enrolled from April 2018 to April 2019 in the context of a prospective, placebo-controlled, double-blind study. Women were randomized to receive treatment with either the botanical combination (250 mg daily divided into two doses) or placebo for eight weeks. At the beginning and end of the study, health-related Quality of Life was assessed using the Cervantes Scale. Subjects treated with the botanical extract, compared to subjects in the placebo group, showed a significant improvement in the Global health-related Quality of Life score (38% [11.3–50.0]% vs. 18.8% [0–37.7]%; P = 0.04) on the Cervantes Scale and, specifically, in the menopause and health domain (13.6% [0–45.4]% vs. 40.7% [20.6–61.0]%; P = 0.05). By contrast, there were no significant changes in the psychic, sexuality, and couple relationship related domains of the Cervantes Scale. Patients who concluded the study did not report substantial side effects. Conclusion Short-term intake of the botanical combination improved the Global Quality of Life of climateric women, according to the Cervantes Scale. Since this is a pilot trial, results should be analysed with caution. Trial registration NCT04381026; ClinicalTrial.gov (retrospectively registered).


Author(s):  
Farough Homeirani MSc ◽  
Mohammad Reza Keramati MD ◽  
Mohammad Hadi Sadeghian MD ◽  
Zeynab Mozaffari MSc ◽  
Azam Moradi Zarmehri MD

Background: Recurrent blood transfusion is a common treatment in patients with thalassemia. The development of antibodies against red blood cell (RBC) antigens complicates RBC cross-matching, enhances the in vivo destruction of transfused cells, accelerates tissue iron overloading, delays the provision of safe transfusion, and reduces health-related quality of life. Materials and Methods: In total, 516 thalassemia patients with a mean age of 18.5 years were included in this cross-sectional study in Mashhad University of Medical Sciences, Razavi Khorasan Province, Iran, in cooperation with the Abu Rayhan Special Medical Center and Hormozgan Blood Transfusion Organization between June 2015 and May 2016. The detection and identification of alloantibodies were done using 3 screen cells and 11 panel cells, respectively. To detect autoantibodies, auto-control was performed using polyspecific Coombs (IgG + C3d) standard method. Results: Alloantibodies and autoantibodies were observed in 16 (3.1%) and 21 (4.1%) patients, respectively. Among patients with alloantibodies, 2 patients (12.5%) developed 3 antibodies (Anti-c,E,P1; Anti-c,E,K), 1 patient (6.25%) developed 2 antibodies (Anti-D,C), and 13 patients developed 1 antibody (4 patients Anti-D (25%); 3 Anti-K (18.75%); 2 Anti-E (12.5%); 2 Anti-C (12.5%); 1 Anti-Jka (6.25%); and 1 Anti-Jkb (6.25%)). A statistically significant correlation between patient age (P = 0.031), age of splenectomy (P = 0.006), Rh(D) (P = 0.001), leukoreduction of RBCs (P = 0.043), and type of disease (P = 0.006) with RBC alloimmunization was seen. Conclusions: This study emphasized the need for the determination of RBC minor antigens, especially for Rh, Kell, and Kidd blood group systems, before the first transfusion and transfusion of antigen-matched blood. In addition, transfusion of prestorage leukoreduced packed cells is recommended for these patients. Keywords: Alloimmunization, Autoimmunization, Blood Transfusion, Thalassemia


2014 ◽  
Vol 64 (3) ◽  
pp. 299-309 ◽  
Author(s):  
Aly H. Nada ◽  
Abdelazim A. Zaghloul ◽  
Mohsen M. Hedaya ◽  
Ibrahim S. Khattab

Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large molecular mass. The aim of the present study was to develop alpha-tocopherol (T) topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001-0.015 %). Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO), tocopheryl polyethylene glycols (TPGs), propylene glycol, ethanol and 9.5 % T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 μg g-1, respectively. Increasing T concentration from 4.8 to 9.5 % did not increase the amount permeated or % of T retained. It was concluded that simple solutions of T in the presence of DMSO and TPGs were more promising systems for effective transdermal permeation compared to gel, emulsion or oleaginous systems.


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