Search results for "RELEASE"
showing 10 items of 602 documents
Deciphering the Nonsense Readthrough Mechanism of Action of Ataluren: An in Silico Compared Study
2019
Ataluren was reported to suppress nonsense mutations by promoting the readthrough of premature stop codons, although its mechanism of action (MOA) is still debated. The likely interaction of Ataluren with CFTR-mRNA has been previously studied by molecular dynamics. In this work we extended the modeling of Ataluren's MOA by complementary computational approaches such as induced fit docking (IFD), quantum polarized ligand docking (QPLD), MM-GBSA free-energy calculations, and computational mutagenesis. In addition to CFTR-mRNA, this study considered other model targets implicated in the translation process, such as eukaryotic rRNA 18S, prokaryotic rRNA 16S, and eukaryotic Release Factor 1 (eRF…
In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model.
2015
Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR…
In situ formation of steroidal supramolecular gels designed for drug release
2013
In this work, a steroidal gelator containing an imine bond was synthesized, and its gelation behavior as well as a sensitivity of its gels towards acids was investigated. It was shown that the gels were acid-responsive, and that the gelator molecules could be prepared either by a conventional synthesis or directly in situ during the gel forming process. The gels prepared by both methods were studied and it was found that they had very similar macroand microscopic properties. Furthermore, the possibility to use the gels as carriers for aromatic drugs such as 5-chloro-8-hydroxyquinoline, pyrazinecarboxamide, and antipyrine was investigated and the prepared two-component gels were studied with…
In vitro evaluation of poloxamer in situ forming gels for bedaquiline fumarate salt and pharmacokinetics following intramuscular injection in rats
2019
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Boosting the in situ encapsulation of proteins with MIL-100(Fe): the role of strong Lewis acid centers
2021
Encapsulation of biomolecules using Metal-Organic Frameworks (MOFs) to form stable biocomposites has been demonstrated a valuable strategy for their preservation and controlled release, which has been however restricted to specific electrostatic surface conditions. We present a general in situ strategy that promotes the spontaneous MOF growth onto a broad variety of proteins, for the first time, regardless of their surface nature. We demonstrate that MOFs based on cations exhibiting considerable inherent acidity such as MIL-100(Fe) enable biomolecule encapsulation, including alkaline proteins previously inaccesible by the welldeveloped in situ encapsulation with azolate-based MOFs. In parti…
Defining level A IVIVC dissolution specifications based on individual in vitro dissolution profiles of a controlled release formulation.
2018
Regulatory guidelines recommend that, when a level A IVIVC is established, dissolution specification should be established using averaged data and the maximum difference between AUC and Cmax between the reference and test formulations cannot be greater than 20%. However, averaging data assumes a loss of information and may reflect a bias in the results. The objective of the current work is to present a new approach to establish dissolution specifications using a new methodology (individual approach) instead of average data (classical approach). Different scenarios were established based on the relationship between in vitro-in vivo dissolution rate coefficient using a level A IVIVC of a cont…
Advocacy of targeting protease‐activated receptors in severe coronavirus disease 2019
2021
Identifying drug targets mitigating vascular dysfunction, thrombo-inflammation and thromboembolic complications in COVID-19 is essential. COVID-19 coagulopathy differs from sepsis coagulopathy. Factors that drive severe lung pathology and coagulation abnormalities in COVID-19 are not understood. Protein-protein interaction studies indicate that the tagged viral bait protein ORF9c directly interacts with PAR2, which modulates host cell IFN and inflammatory cytokines. In addition to direct interaction of SARS-CoV-2 viral protein with PARs, we speculate that activation of PAR by proteases plays a role in COVID-19-induced hyperinflammation. In COVID-19-associated coagulopathy elevated levels of…
The second data release of the INT Photometric Hα Survey of the Northern Galactic Plane (IPHAS DR2)
2014
The INT/WFC Photometric H-Alpha Survey of the Northern Galactic Plane (IPHAS) is a 1800 square degrees imaging survey covering Galactic latitudes |b| < 5 deg and longitudes l = 30 to 215 deg in the r, i and H-alpha filters using the Wide Field Camera (WFC) on the 2.5-metre Isaac Newton Telescope (INT) in La Palma. We present the first quality-controlled and globally-calibrated source catalogue derived from the survey, providing single-epoch photometry for 219 million unique sources across 92% of the footprint. The observations were carried out between 2003 and 2012 at a median seeing of 1.1 arcsec (sampled at 0.33 arcsec/pixel) and to a mean 5\sigma-depth of 21.2 (r), 20.0 (i) and 20.3 (H-a…
Luminescent PhotoCORMs: Enabling/Disabling CO Delivery upon Blue Light Irradiation.
2020
The new luminescent carbonyl compounds [Mn(Oxa-H)(CO)3Br] (1) and [Mn(Oxa-NMe2)(CO)3Br] (2) were synthesized and fully characterized. Complexes 1 and 2 showed CO release under blue light (λ453). Spectroscopic techniques and TD-DFT and SOC-TD-DFT calculations indicated that 1 and 2 release the Oxa-H and Oxa-NMe2 coligands in addition to the carbonyl ligands, increasing the luminescence during photoinduction.
Self-Immolative Linkers as Caps for the Design of Gated Silica Mesoporous Supports
2016
A new hybrid material based on sulforhodamine-B dye-loaded silica mesoporous nanoparticles capped with a self-immolative gate has been synthesized and characterized. The gated material's controlled release behavior is monitored under different pH conditions. Under acidic and neutral conditions, a low level of dye release is detected. However, at slightly basic pH, significant dye release occurs owing to deprotonation of the phenol moiety in the capping molecule, which results in its disassembly.