Heat-based transdermal delivery of a ramipril loaded cream for treating hypertension

Anna Voronova (1, 2) , Quentin Pagneux (2, 1) , Raphael Decoin (3, 4) , Eloise Woitrain (3, 4) , Laura Butruille (3, 4) , Alexandre Barras (2, 1) , Catherine Foulon (5) , Marie Lecoeur (5) , Diego Jaramillo (6) , José Rumipamba (6) , Sorin Melinte (6) , Amar Abderrahmani (1, 2) , David Montaigne (4, 3) , Rabah Boukherroub (1, 2) , Sabine Szunerits (1, 2)

1 IEMN - Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520
2 NBI - IEMN - NanoBioInterfaces - IEMN
3 EGID - Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508
4 RNMCD - Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011
5 GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365
6 UCL - Université Catholique de Louvain = Catholic University of Louvain

Angiotensin-converting enzyme (ACE) inhibitors play an important role in the development of anti-hypertension approaches, with ramipril being one of the most widely used ACE inhibitor prodrugs orally administered once or twice a day. Due to its low bioavailability, large amounts have to be administered to obtain a therapeutic effect. In this work, we propose a ramipril loaded pharmaceutical formulation in contact with an electrothermal actuator based on a gold nanohole array as an efficient approach to increase the transdermal ramipril flux. Using rats as an in vivo model, the effect on the systolic and diastolic blood pressure is evaluated, showing that under optimized conditions the blood pressure could be regulated. Heat activation resulted in total drug delivery out of a bandage loaded with 1 mg ramipril, revealing a flux of 50.9 +/- 2.8 mu g cm(-2) h(-1). Importantly, heat-based transdermal dispensing allowed efficient and rapid delivery of ramipril in spontaneously hypertensive rats, with its active form (ramiprilat) detected in blood as early as 5 minutes after delivery onset, accompanied by significant decrease in blood pressure.

Domaines: Sciences de l'ingénieur [physics]

Anna Voronova, Quentin Pagneux, Raphael Decoin, Eloise Woitrain, Laura Butruille, et al.. Heat-based transdermal delivery of a ramipril loaded cream for treating hypertension. Nanoscale, 2022, 14 (34), pp.12247-12256. ⟨10.1039/d2nr02295h⟩. ⟨hal-03764623⟩