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• W4200503509 endingPage "106108" @default.
• W4200503509 startingPage "106108" @default.
• W4200503509 abstract "Hypertension is a chronic pathology where blood pressure levels are continuously high, causing cardiac, renal, cerebral, and vascular damage leading to early morbi-mortality. This illness is the main risk factor for cardiovascular diseases and the main cause of atrial fibrillation. Atenolol (AT) is a β-1 blocker drug useful for antihypertension and antiarrhythmic treatments. However, this drug possesses low oral bioavailability associated to its low permeability and extensive hepatic first-pass metabolism. To solve the conventional AT-administration problems, oral controlled-release and transdermal delivery have been reported. In this work, an alternative AT inhalatory system administered by nebulization is presented. This system is based on an ionic complex between acidic groups of alginic acid and cationic groups of AT (AA-AT), which was obtained by spray-drying. Pharmaceutical and biopharmaceutical properties for AA-AT inhalatory administration using a jet nebulizer were investigated. The aerodynamic performance (assayed at different cup-nebulizer loadings) of the nebulized system demonstrated that around 40% of the formulation would deposit in the respiratory membrane, with mass median aerodynamic diameters of 3.4-3.6 µm. The AT carried in the AA-AT system was released adequately by ionic exchange in saline solution by permeation through a cellulose membrane. The presence of AA as polyelectrolyte conferred mucoadhesive properties to the ionic complex. Even at high relative AA-AT concentrations, no cytotoxic effect was detected in A-549 cell line. Finally, the preliminary pharmacokinetic assay in the in vivo model confirmed that AT was absorbed from the lung to the systemic circulation, with a greater plasmatic AUC compared to the pure drug (around 50% higher). Then, the system and the nebulization administration demonstrated potential for drug cardiac targeting." @default.
• W4200503509 created "2021-12-31" @default.
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• W4200503509 date "2022-03-01" @default.
• W4200503509 modified "2023-10-14" @default.
• W4200503509 title "Nebulization of a polyelectrolyte-drug system for systemic hypertension treatment" @default.
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• W4200503509 doi "https://doi.org/10.1016/j.ejps.2021.106108" @default.
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