2 research outputs found
Mechanistic Investigation of Inclusion Complexes of a Sulfa Drug with α- and β‑Cyclodextrins
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
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