Oral delivery of ambrisentan-loaded lipid-core nanocapsules as a novel approach for the treatment of pulmonary arterial hypertension

• Published in: International journal of pharmaceutics Vol. 610; p. 121181
• Main Authors: Zancan, Lali Ronsoni, Bruinsmann, Franciele Aline, Paese, Karine, Türck, Patrick, Bahr, Alan, Zimmer, Alexsandra, Carraro, Cristina Campos, Schenkel, Paulo Cavalheiro, Belló-Klein, Adriane, Schwertz, Claiton I., Driemeier, David, Pohlmann, Adriana Raffin, Guterres, Sílvia Stanisçuaski
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-12-2021
• Subjects: Ambrisentan; Animals; Female; Hypertension, Pulmonary - drug therapy; In vivo; Lipid-core nanocapsules; Lipids; Monocrotaline-induced model; Nanocapsules - therapeutic use; Nanotechnology; Phenylpropionates; Pulmonary Arterial Hypertension; Pyridazines; Rats; In vivo; Monocrotaline-induced model; Pulmonary arterial hypertension; Nanotechnology; Lipid-core nanocapsules; Ambrisentan
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.121181

[Display omitted]
Ambrisentan (AMB) is an orphan drug approved for oral administration that has been developed for the treatment of pulmonary arterial hypertension (PAH), a chronic and progressive pathophysiological state that might result in death if left untreated. Lipid-core nanocapsules (LNCs) are versatile nanoformulations capable of loading lipophilic drugs for topical, vaginal, oral, intravenous, pulmonary, and nasal administration. Our hypothesis was to load AMB into these nanocapsules (LNCamb) and test their effect on slowing or reducing the progression of monocrotaline-induced PAH in a rat model, upon oral administration. LNCamb displayed a unimodal distribution of diameters (around 200 nm), negative zeta potential (–11.5 mV), high encapsulation efficiency (78%), spherical shape, and sustained drug release (50–60% in 24 h). The in vivo pharmacodynamic effect of the LNCamb group was evaluated by observing the echocardiography, hemodynamic, morphometric, and histological data, which showed a significant decrease in PAH in this group, as compared to the control group (AMBsolution). LNCamb showed the benefit of reversing systolic dysfunction and preventing vascular remodeling with greater efficacy than that observed in the control group. The originality and contribution of our work reveal the promising value of this nanoformulation as a novel therapeutic strategy for PAH treatment.