ArticleAmerican journal of physiology. Lung cellular and molecular physiology2019
Inhaled combination of sildenafil and rosiglitazone improves pulmonary hemodynamics, cardiac function, and arterial remodeling.
Article in American journal of physiology. Lung cellular and molecular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Fundamental and Targeted Approaches in Pulmonary Arterial Hypertension Treatment.Pharmaceutics · 2025Review
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Unleashing the Potential of Nrf2: A Novel Therapeutic Target for Pulmonary Vascular Remodeling.Antioxidants (Basel, Switzerland) · 2023Review
- Article
- Drugs against metabolic diseases as potential senotherapeutics for aging-related respiratory diseases.Frontiers in endocrinology · 2023Review
- Early diagnosis and targeted approaches to pulmonary vascular disease in bronchopulmonary dysplasia.Pediatric research · 2022Review
- Xinmai 'an extract enhances the efficacy of sildenafil in the treatment of pulmonary arterial hypertension via inhibiting MAPK signalling pathway.Pharmaceutical biology · 2021Article
- Taking it to heart: dissecting cardiopulmonary interactions in diseases of the lung and the cardiovascular system.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Newer approaches and novel drugs for inhalational therapy for pulmonary arterial hypertension.Expert opinion on drug delivery · 2020Review
- PulmoBind Imaging Measures Reduction of Vascular Adrenomedullin Receptor Activity with Lack of effect of Sildenafil in Pulmonary Hypertension.Scientific reports · 2019Article
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Currently, dual- or triple-drug combinations comprising different vasodilators are the mainstay for the treatment of pulmonary arterial hypertension (PAH). However, the patient outcome continues to be disappointing because the existing combination therapy cannot restrain progression of the disease. Previously, we have shown that when given as a monotherapy, long-acting inhaled formulations of sildenafil (a phosphodiesterase-5 inhibitor) and rosiglitazone (a peroxisome proliferator receptor-γ agonist) ameliorate PAH in rats. Thus, with a goal to develop a new combination therapy, we prepared and characterized poly(lactic-co-glycolic acid) (PLGA)-based long-acting inhalable particles of sildenafil and rosiglitazone. We then assessed the efficacy of the combinations of sildenafil and rosiglitazone, given in plain forms or as PLGA particles, in reducing mean pulmonary arterial pressure (mPAP) and improving pulmonary arterial remodeling and right ventricular hypertrophy (RVH) in Sugen 5416 plus hypoxia-induced PAH rats. After intratracheal administration of the formulations, we catheterized the rats and measured mPAP, cardiac output, total pulmonary resistance, and RVH. We also conducted morphometric studies using lung tissue samples and assessed the degree of muscularization, the arterial medial wall thickening, and the extent of collagen deposition. Compared with the plain drugs, given via the pulmonary or oral route as a single or dual combination, PLGA particles of the drugs, although given at a longer dosing interval compared with the plain drugs, caused more pronounced reduction in mPAP without affecting mean systemic pressure, improved cardiac function, slowed down right heart remodeling, and reduced arterial muscularization. Overall, PLGA particles of sildenafil and rosiglitazone, given as an inhaled combination, could be a viable alternative to currently available vasodilator-based combination therapy for PAH.
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