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

Author(s):Show less -

Zancan, Lali Ronsoni ^[1] ; Bruinsmann, Franciele Aline ^[2] ; Paese, Karine ^[2] ; Turck, Patrick ^[3] ; Bahr, Alan ^[3] ; Zimmer, Alexsandra ^[3] ; Carraro, Cristina Campos ^[3] ; Schenkel, Paulo Cavalheiro ^[3] ; Bello-Klein, Adriane ^[3] ; Schwertz, I, Claiton ; Driemeier, David ^[4] ; Pohlmann, Adriana Raffin ^[2] ; Guterres, Silvia Staniscuaski ^{[1, 2]}

Affiliation

^[1] Univ Fed Rio Grande Sul UFRGS, Programa Posgrad Nanotecnol, Av Ipiranga 2752, BR-90610000 Porto Alegre, RS - Brazil

^[2] Univ Fed Rio Grande Sul UFRGS, Programa Posgrad Ciencias Farmaceut, Av Ipiranga 2752, BR-90610000 Porto Alegre, RS - Brazil

^[3] Univ Fed Rio Grande Sul UFRGS, Lab Fisiol Cardiovasc & Especies Ativas Oxigenio, Rua Sarmento Leite 500, BR-90050170 Porto Alegre, RS - Brazil

^[4] Schwertz, Claiton, I, Univ Fed Rio Grande Sul UFRGS, Fac Vet, Dept Patol Clin Vet, Setor Patol Vet, Av Bento Goncalves 9090, BR-91540000 Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 610, DEC 15 2021.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants