ArticleJournal of controlled release : official journal of the Controlled Release Society2017
Inhaled sildenafil as an alternative to oral sildenafil in the treatment of pulmonary arterial hypertension (PAH).
Article in Journal of controlled release : official journal of the Controlled Release Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 57 citations in OpenAlex.
- Biochemical and clinical effects of continuous positive airway pressure combined with sildenafil on inflammatory and hemodynamic profiles in obese asthma patients with pulmonary arterial hypertension.Journal of medical biochemistry · 2026Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Fundamental and Targeted Approaches in Pulmonary Arterial Hypertension Treatment.Pharmaceutics · 2025Review
- Next-generation pediatric care: nanotechnology-based and AI-driven solutions for cardiovascular, respiratory, and gastrointestinal disorders.World journal of pediatrics : WJP · 2025Review
- Platelet Membrane-Encapsulated Poly(lactic-International journal of pharmaceutics: X · 2024Article
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Inhaled Pulmonary Vasodilators for the Treatment of Right Ventricular Failure in Cardio-Thoracic Surgery: Is One Better than the Others?Journal of clinical medicine · 2024Review
- Article
- Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks.Drug delivery · 2021Article
- Update on the use of sildenafil in neonatal pulmonary hypertension: a narrative review of the history, current administration, and future directions.Translational pediatrics · 2021Review
- Newer approaches and novel drugs for inhalational therapy for pulmonary arterial hypertension.Expert opinion on drug delivery · 2020Review
- Pre-clinical assessment of a water-in-fluorocarbon emulsion for the treatment of pulmonary vascular diseases.Drug delivery · 2019Article
- PulmoBind Imaging Measures Reduction of Vascular Adrenomedullin Receptor Activity with Lack of effect of Sildenafil in Pulmonary Hypertension.Scientific reports · 2019Article
- Inhaled combination of sildenafil and rosiglitazone improves pulmonary hemodynamics, cardiac function, and arterial remodeling.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Repurposing rosiglitazone, a PPAR-γ agonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The practice of treating PAH patients with oral or intravenous sildenafil suffers from the limitations of short dosing intervals, peripheral vasodilation, unwanted side effects, and restricted use in pediatric patients. In this study, we sought to test the hypothesis that inhalable poly(lactic-co-glycolic acid) (PLGA) particles of sildenafil prolong the release of the drug, produce pulmonary specific vasodilation, reduce the systemic exposure of the drug, and may be used as an alternative to oral sildenafil in the treatment of PAH. Thus, we prepared porous PLGA particles of sildenafil using a water-in-oil-in-water double emulsion solvent evaporation method with polyethyleneimine (PEI) as a porosigen and characterized the formulations for surface morphology, respirability, in-vitro drug release, and evaluated for in vivo absorption, alveolar macrophage uptake, and safety. PEI increased the particle porosity, drug entrapment, and produced drug release for 36h. Fluorescent particles showed reduced uptake by alveolar macrophages. The polymeric particles were safe to rat pulmonary arterial smooth muscle cell and to the lungs, as evidenced by the cytotoxicity assay and analyses of the injury markers in the bronchoalveolar lavage fluid, respectively. Intratracheally administered sildenafil particles elicited more pulmonary specific and sustained vasodilation in SUGEN-5416/hypoxia-induced PAH rats than oral, intravenous, or intratracheal plain sildenafil did, when administered at the same dose. Overall, true to the hypothesis, this study shows that inhaled PLGA particles of sildenafil can be administered, as a substitute for oral form of sildenafil, at a reduced dose and longer dosing interval.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.