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

被引：12

作者：

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, Claiton, I ^{[4
]}

Driemeier, David ^{[4
]}

Pohlmann, Adriana Raffin ^{[2
]}

Guterres, Silvia Staniscuaski ^{[1
,2
]}

机构：

[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] 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

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2021年 / 610卷

基金：

巴西圣保罗研究基金会;

关键词：

Nanotechnology; Lipid-core nanocapsules; Ambrisentan; Pulmonary arterial hypertension; In vivo; Monocrotaline-induced model; RIGHT HEART; POLYMERIC NANOPARTICLES; EUROPEAN ASSOCIATION; SUSTAINED-RELEASE; AMERICAN SOCIETY; OXIDATIVE STRESS; RESVERATROL; STABILITY; ECHOCARDIOGRAPHY; ENCAPSULATION;

D O I：

10.1016/j.ijpharm.2021.121181

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页数：11