A Supramolecular Thermosensitive Gel of Ketoconazole for Ocular Applications: In Silico, In Vitro, and Ex Vivo Studies

2021 ◽  
pp. 121409
Author(s):  
Pinal Chaudhari ◽  
Ranjitha Naik ◽  
Lakshmi Sruthi Mallela ◽  
Sanhita Roy ◽  
Sumit Birangal ◽  
...  
Keyword(s):  
In Silico ◽  
Ex Vivo ◽  
Thermosensitive Gel

In Vitro, In Silico and Ex Vivo Studies of Dihydroartemisinin Derivatives as Antitubercular Agents

2019 ◽  
Vol 19 (8) ◽  
pp. 633-644 ◽  
Author(s):  
Komal Kalani ◽  
Sarfaraz Alam ◽  
Vinita Chaturvedi ◽  
Shyam Singh ◽  
Feroz Khan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Silico ◽  
Ex Vivo ◽  
Virulent Strain ◽  
Infection Model ◽  
Mouse Bone Marrow ◽  
Significant Activity ◽  
Macrophage Infection ◽  
In Silico Studies

Introduction: As a part of our drug discovery program for anti-tubercular agents, dihydroartemisinin (DHA-1) was screened against Mtb H37Rv, which showed moderate anti-tubercular activity (>25.0 µg/mL). These results prompted us to carry out the chemical transformation of DHA-1 into various derivatives and study their antitubercular potential. Materials and Methods: DHA-1 was semi-synthetically converted into four new acyl derivatives (DHA-1A – DHA-1D) and in-vitro evaluated for their anti-tubercular potential against Mycobacterium tuberculosis H37Rv virulent strain. The derivatives, DHA-1C (12-O-(4-nitro) benzoyl; MIC 12.5 µg/mL) and DHA-1D (12-O-chloro acetyl; MIC 3.12µg/mL) showed significant activity against the pathogen. Results: In silico studies of the most active derivative (DHA-1D) showed interaction with ARG448 inhibiting the mycobacterium enzymes. Additionally, it showed no cytotoxicity towards the Vero C1008 cells and Mouse bone marrow derived macrophages. Conclusion: DHA-1D killed 62% intracellular M. tuberculosis in Mouse bone marrow macrophage infection model. To the best of our knowledge, this is the first-ever report on the antitubercular potential of dihydroartemisinin and its derivatives. Since dihydroartemisinin is widely used as an antimalarial drug; these results may be of great help in anti-tubercular drug development from a very common, inexpensive, and non-toxic natural product.

Aryl Maleimides as Apoptosis Inducers on L5178-Y Murine Leukemia Cells (in silico, in vitro and ex vivo Study)

2016 ◽  
Vol 16 (12) ◽  
pp. 1615-1621 ◽  
Author(s):  
Erik Andrade-Jorge ◽  
Marycarmen Godínez-Victoria ◽  
Luvia Enid Sánchez-Torres ◽  
Luis Humberto Fabila-Castillo ◽  
José G. Trujillo-Ferrara
Keyword(s):  
In Silico ◽  
Ex Vivo ◽  
Leukemia Cells ◽  
Ex Vivo Study ◽  
Murine Leukemia

scholarly journals In Silico Predicted Antifungal Peptides: In Vitro and In Vivo Anti-Candida Activity

2021 ◽  
Vol 7 (6) ◽  
pp. 439
Author(s):  
Tecla Ciociola ◽  
Walter Magliani ◽  
Tiziano De Simone ◽  
Thelma A. Pertinhez ◽  
Stefania Conti ◽  
...  
Keyword(s):  
In Silico ◽  
Mammalian Cells ◽  
Galleria Mellonella ◽  
Ex Vivo ◽  
Consensus Sequence ◽  
In Silico Analysis ◽  
Significant Activity ◽  
Synthetic Antibody

It has been previously demonstrated that synthetic antibody-derived peptides could exert a significant activity in vitro, ex vivo, and/or in vivo against microorganisms and viruses, as well as immunomodulatory effects through the activation of immune cells. Based on the sequence of previously described antibody-derived peptides with recognized antifungal activity, an in silico analysis was conducted to identify novel antifungal candidates. The present study analyzed the candidacidal and structural properties of in silico designed peptides (ISDPs) derived by amino acid substitutions of the parent peptide KKVTMTCSAS. ISDPs proved to be more active in vitro than the parent peptide and all proved to be therapeutic in Galleria mellonella candidal infection, without showing toxic effects on mammalian cells. ISDPs were studied by circular dichroism spectroscopy, demonstrating different structural organization. These results allowed to validate a consensus sequence for the parent peptide KKVTMTCSAS that may be useful in the development of novel antimicrobial molecules.

Synthesis and characterization of Chitosan-Catechol conjugates: Development and in vitro, in silico and in vivo evaluation of mucoadhesive pellets of lafutidine

2021 ◽  
pp. 088391152199784
Author(s):  
Loveleen Kaur ◽  
Ajay Kumar Thakur ◽  
Pradeep Kumar ◽  
Inderbir Singh
Keyword(s):  
Drug Release ◽  
In Silico ◽  
Ex Vivo ◽  
Strong Interactions ◽  
Dissolution Time ◽  
Sem Images ◽  
In Vivo Evaluation ◽  
Release Studies

Present study was aimed to synthesize and characterize Chitosan-Catechol conjugates and to design and develop mucoadhesive pellets loaded with lafutidine. SEM images indicated the presence of fibrous structures responsible for enhanced mucoadhesive potential of Chitosan-Catechol conjugates. Thermodynamic stability and amorphous nature of conjugates was confirmed by DSC and XRD studies respectively. Rheological studies were used to evaluate polymer mucin interactions wherein strong interactions between Chitosan-Catechol conjugate and mucin was observed in comparison to pristine chitosan and mucin. The mucoadhesion potential of Chitosan-Catechol (Cht-C) versus Chitosan (Cht) was assessed in silico using molecular mechanics simulations and the results obtained were compared with the in vitro and ex vivo results. Cht-C/mucin demonstrated much higher energy stabilization (∆E ≈ −65 kcal/mol) as compared to Cht/mucin molecular complex. Lafutidine-loaded pellets were prepared from Chitosan (LPC) and Chitosan-Catechol conjugates (LPCC) and were evaluated for various physical properties viz. flow, circularity, roundness, friability, drug content, particle size and percent mucoadhesion. In vitro drug release studies on LPC and LPCC pellets were performed for computing t50%, t90% and mean dissolution time. The values of release exponent from Korsmeyer-Peppas model was reported to be 0.443 and 0.759 for LPC and LPCC pellets suggesting Fickian and non-Fickian mechanism representing drug release, respectively. In vivo results depicted significant controlled release and enhanced residence of the drug after being released from the chitosan-catechol coated pellets. Chitosan-Catechol conjugates were found to be a promising biooadhesive polymer for the development of various mucoadhesive formulations.

A Dual-Biotic System for the Concurrent Delivery of Antibiotics and Probiotics: In Vitro, Ex Vivo, In Vivo and In Silico Evaluation and Correlation

2016 ◽  
Vol 33 (12) ◽  
pp. 3057-3071 ◽  
Author(s):  
Mershen Govender ◽  
Yahya E. Choonara ◽  
Sandy van Vuuren ◽  
Pradeep Kumar ◽  
Lisa C. du Toit ◽  
...  
Keyword(s):  
In Silico ◽  
Ex Vivo

scholarly journals How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 675 ◽  
Author(s):  
Mariana Amaral ◽  
Ana Sofia Martins ◽  
José Catarino ◽  
Pedro Faísca ◽  
Pradeep Kumar ◽  
...  
Keyword(s):  
In Silico ◽  
Ex Vivo ◽  
Polymeric Nanoparticles ◽  
Spherical Shape ◽  
Diabetic Rats ◽  
Laser Scattering ◽  
In Vivo Models ◽  
Mean Size

Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach’s low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats’ glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery.

scholarly journals Avant-propos

2019 ◽  
Vol 35 (2) ◽  
pp. 152-152
Author(s):  
Thierry Jouault
Keyword(s):  
Caenorhabditis Elegans ◽  
In Silico ◽  
Ex Vivo

Pour éclairer la série que nous vous proposons, il nous a semblé important de rappeler les règles définissant ce que sont les organismes-modèles ainsi que la réglementation en vigueur quant à leur utilisation en recherche biomédicale. Les études in vitro ou ex vivo, sur cellules ou tissus, ou les analyses in silico ne permettent pas d’aborder des problématiques complexes. Elles sont certes utiles pour des analyses mécanistiques, mais ne permettent pas l’étude de réponses biologiques intégrées qui nécessitent l’analyse d’un organisme entier. Ces organismes sont soumis à une réglementation stricte. Elle les distingue selon qu’ils sont vertébrés ou invertébrés. Si les mammifères modélisent nombre de pathologies humaines, certains organismes simples permettent également de mener ce type d’études et de répondre à des questions liées à la génétique. Leur intérêt est leur rapidité et leur capacité de reproduction qui facilitent les expérimentations. Le poisson zèbre en est un bon exemple avec les nombreuses versions de morphants qui ont été développés et qui ont permis de révéler les conséquences d’altérations génomiques sur un phénotype particulier. Cet organisme-modèle est donc particulièrement utilisé pour l’étude de pathologies monogéniques ou pour déterminer le rôle d’un gène dans l’étiologie de diverses pathologies. La transparence du poisson zèbre rend de plus les investigations plus faciles. Caenorhabditis elegans est également un excellent modèle d’organisme simple et qui, contrairement au poisson zèbre, ne relève pas de la réglementation concernant l’expérimentation animale. Son utilisation est ainsi, comme pour les insectes, plus aisée. Connaître les différences entre les organismes-modèles, leurs avantages et leurs limites, et les règles dictant leur utilisation est donc primordial pour la réalisation d’expérimentations qui restent nécessaires à l’acquisition de nouvelles connaissances dans le domaine de la biologie et de la santé.

scholarly journals ADAM22/LGI1 complex as a new actionable target for breast cancer brain metastasis

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Sara Charmsaz ◽  
Ben Doherty ◽  
Sinéad Cocchiglia ◽  
Damir Varešlija ◽  
Attilio Marino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
In Silico ◽  
Ex Vivo ◽  
Metastatic Breast ◽  
Peptide Mimetic ◽  
Breast Cancer Brain Metastasis

Abstract Background Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood–brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets. Methods Global transcriptomic analysis of matched primary and metastatic patient tumours (n = 35 patients, 70 tumour samples) identified a putative new actionable target for advanced breast cancer which was further validated in vivo and in breast cancer patient tumour tissue (n = 843 patients). A peptide mimetic of the target’s natural ligand was designed in silico and its efficacy assessed in in vitro, ex vivo and in vivo models of breast cancer metastasis. Results Bioinformatic analysis of over-represented pathways in metastatic breast cancer identified ADAM22 as a top ranked member of the ECM-related druggable genome specific to brain metastases. ADAM22 was validated as an actionable target in in vitro, ex vivo and in patient tumour tissue (n = 843 patients). A peptide mimetic of the ADAM22 ligand LGI1, LGI1MIM, was designed in silico. The efficacy of LGI1MIM and its ability to penetrate the BBB were assessed in vitro, ex vivo and in brain metastasis BBB 3D biometric biohybrid models, respectively. Treatment with LGI1MIM in vivo inhibited disease progression, in particular the development of brain metastasis. Conclusion ADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.

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