Display options
Cite
Ceschan NE, Scioli-Montoto S, Sbaraglini ML, et al. Nebulization of a polyelectrolyte-drug system for systemic hypertension treatment. Eur J Pharm Sci. 2021;170:106108doi: 10.1016/j.ejps.2021.106108.
Ceschan, N. E., Scioli-Montoto, S., Sbaraglini, M. L., Ruiz, M. E., Smyth, H. D. C., Bucalá, V., & Ramírez-Rigo, M. V. (2021). Nebulization of a polyelectrolyte-drug system for systemic hypertension treatment. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 170106108. https://doi.org/10.1016/j.ejps.2021.106108
Ceschan, Nazareth E, et al. "Nebulization of a polyelectrolyte-drug system for systemic hypertension treatment." European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences vol. 170 (2021): 106108. doi: https://doi.org/10.1016/j.ejps.2021.106108
Ceschan NE, Scioli-Montoto S, Sbaraglini ML, Ruiz ME, Smyth HDC, Bucalá V, Ramírez-Rigo MV. Nebulization of a polyelectrolyte-drug system for systemic hypertension treatment. Eur J Pharm Sci. 2021 Dec 26;170:106108. doi: 10.1016/j.ejps.2021.106108. Epub 2021 Dec 26. PMID: 34963620.
Copy Download .nbib Format: NLM
Share it on

Eur J Pharm Sci. 2021 Dec 26;170:106108. doi: 10.1016/j.ejps.2021.106108. Epub 2021 Dec 26.

Nebulization of a polyelectrolyte-drug system for systemic hypertension treatment.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

Nazareth E Ceschan, Sebastián Scioli-Montoto, María Laura Sbaraglini, María Esperanza Ruiz, Hugh D C Smyth, Verónica Bucalá, María V Ramírez-Rigo

Affiliations

  1. Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET - Universidad Nacional del Sur (UNS), Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia, UNS, San Juan 670, 8000 Bahía, Blanca, Argentina. Electronic address: [email protected].
  2. Laboratory of Bioactive Research and Development (LIDeB), Faculty of Exact Sciences, Universidad Nacional de La Plata (UNLP).
  3. College of Pharmacy, The University of Texas at Austin, 2409 West University Avenue, Austin, TX, United States.
  4. Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET - Universidad Nacional del Sur (UNS), Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina; Departamento de Ingeniería Química, UNS, Avenida Alem 1253, 8000 Bahía, Blanca, Argentina.
  5. Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET - Universidad Nacional del Sur (UNS), Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia, UNS, San Juan 670, 8000 Bahía, Blanca, Argentina.

PMID: 34963620 DOI: 10.1016/j.ejps.2021.106108

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.

Copyright © 2021. Published by Elsevier B.V.

Keywords: Aerosolization behavior; Cell viability; Mucoadhesiveness; Pharmacokinetics; Polyelectrolyte-drug formulation

Publication Types