2 research outputs found

    Mechanistic Investigation of Inclusion Complexes of a Sulfa Drug with α- and β‑Cyclodextrins

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    Molecular encapsulation is extremely important in pharmaceutical and drug delivery science. In this article, one of the most important sulfa drugs, namely, sulfacetamide sodium, has been probed in the solution and solid phases for encapsulation within the cavities of α- and β-cyclodextrins. Various physicochemical techniques were employed to establish the outcome of the work. The isothermal titration calorimetric method was used to evaluate the stoichiometry, association constant, and thermodynamic parameters with high accuracy. The solid inclusion complexes were analyzed by spectroscopic techniques to ascertain the encapsulation of the investigated drug within the cavities of α- and β-cyclodextrins. This phenomenon of drug inclusion is exceedingly significant for its stabilization against external hazards, such as oxidation, sensitization, and photolytic cleavage, for the proficient and accurate regulatory release of an essential amount of drug at the targeted site for a period of time and for the prevention of overdose when applied as an ophthalmic solution and ointment

    Table1_In-silico drug trials for precision medicine in atrial fibrillation: From ionic mechanisms to electrocardiogram-based predictions in structurally-healthy human atria.DOCX

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    Atrial fibrillation (AF) inducibility, sustainability and response to pharmacological treatment of individual patients are expected to be determined by their ionic current properties, especially in structurally-healthy atria. Mechanisms underlying AF and optimal cardioversion are however still unclear. In this study, in-silico drug trials were conducted using a population of human structurally-healthy atria models to 1) identify key ionic current properties determining AF inducibility, maintenance and pharmacological cardioversion, and 2) compare the prognostic value for predicting individual AF cardioversion of ionic current properties and electrocardiogram (ECG) metrics. In the population of structurally-healthy atria, 477 AF episodes were induced in ionic current profiles with both steep action potential duration (APD) restitution (eliciting APD alternans), and high excitability (enabling propagation at fast rates that transformed alternans into discordant). High excitability also favored 211 sustained AF episodes, so its decrease, through prolonged refractoriness, explained pharmacological cardioversion. In-silico trials over 200 AF episodes, 100 ionic profiles and 10 antiarrhythmic compounds were consistent with previous clinical trials, and identified optimal treatments for individual electrophysiological properties of the atria. Algorithms trained on 211 simulated AF episodes exhibited >70% accuracy in predictions of cardioversion for individual treatments using either ionic current profiles or ECG metrics. In structurally-healthy atria, AF inducibility and sustainability are enabled by discordant alternans, under high excitability and steep restitution conditions. Successful pharmacological cardioversion is predicted with 70% accuracy from either ionic or ECG properties, and it is optimal for treatments maximizing refractoriness (thus reducing excitability) for the given ionic current profile of the atria.</p
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