Evidence map›Paper›PMID 28165252›Full record

ArticleMolecular pharmaceutics2017

Cocktail of Superoxide Dismutase and Fasudil Encapsulated in Targeted Liposomes Slows PAH Progression at a Reduced Dosing Frequency.

Nilesh Gupta, Jahidur Rashid, Eva Nozik-Grayck, Ivan F McMurtry, Kurt R Stenmark, Fakhrul Ahsan

Abstract read
In one paragraph

Article in Molecular pharmaceutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.

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  19. Emerging therapeutics in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Nilesh GuptaDepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center , 1300 Coulter Drive, Amarillo, Texas 79106, United States.
Jahidur RashidDepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center , 1300 Coulter Drive, Amarillo, Texas 79106, United States.
Eva Nozik-GrayckDevelopmental Lung Biology, Cardiovascular Pulmonary Research Laboratories, Division of Pulmonary Sciences and Critical Care Medicine, Division of Pediatrics-Critical Care, Departments of Medicine and Pediatrics, University of Colorado, Denver , Anschutz Medical Campus, Aurora, Colorado 80045, United States.
Ivan F McMurtryDepartments of Pharmacology and Internal Medicine and the Center for Lung Biology, University of South Alabama , Mobile, Alabama 36688, United States.
Kurt R StenmarkDevelopmental Lung Biology, Cardiovascular Pulmonary Research Laboratories, Division of Pulmonary Sciences and Critical Care Medicine, Division of Pediatrics-Critical Care, Departments of Medicine and Pediatrics, University of Colorado, Denver , Anschutz Medical Campus, Aurora, Colorado 80045, United States.
Fakhrul AhsanDepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center , 1300 Coulter Drive, Amarillo, Texas 79106, United States.ORCID 0000-0002-1831-4708
Texas Tech University · USUniversity of Colorado Anschutz Medical Campus · USUniversity of South Alabama · US

Funding

Impact of Insufficient Vascular EC-SOD in Pulmonary HypertensionR01HL086680 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI NOZIK, EVA S. · 2008 to 2017
$4.7M
Targetable and Inhalable Nanoparticle Based Combination Therapy for PAHR01HL114677 · NHLBI · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI AHSAN, FAKHRUL · 2015 to 2018
$1.5M
Anti-PAH Drugs in Inhalable Nanoparticles for Sustained Pulmonary VasodilationR15HL103431 · NHLBI · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI AHSAN, FAKHRUL · 2010 to 2010
$429k
NHLBI NIH HHS R01 HL086680NHLBI NIH HHS R01 HL114677NHLBI NIH HHS R15 HL103431
6 · The paper itself

Abstract

Currently, two or more pulmonary vasodilators are used to treat pulmonary arterial hypertension (PAH), but conventional vasodilators alone cannot reverse disease progression. In this study, we tested the hypothesis that a combination therapy comprising a vasodilator plus a therapeutic agent that slows pulmonary arterial remodeling and right heart hypertrophy is an efficacious alternative to current vasodilator-based PAH therapy. Thus, we encapsulated a cocktail of superoxide dismutase (SOD), a superoxide scavenger, and fasudil, a specific rho-kinase inhibitor, into a liposomal formulation equipped with a homing peptide, CAR. We evaluated the effect of the formulations on pulmonary hemodynamics in monocrotaline-induced PAH rats (MCT-induced PAH) and assessed the formulation's efficacy in slowing the disease progression in Sugen-5416/hypoxia-induced PAH rats (SU/hypoxia-induced PAH). For acute studies, we monitored both mean pulmonary and systemic arterial pressures (mPAP and mSAP) for 2 to 6 h after a single dose of the plain drugs or formulations. In chronic studies, PAH rats received plain drugs every 48 h and the formulations every 72 h for 21 days. In MCT-induced PAH rats, CAR-modified liposomes containing fasudil plus SOD elicited a more pronounced, prolonged, and selective reduction in mPAP than unmodified liposomes and plain drugs did. In SU/hypoxia-induced PAH rats, the formulation produced a >50% reduction in mPAP and slowed right ventricular hypertrophy. When compared with individual plain drugs or combination, CAR-modified-liposomes containing both drugs reduced the extent of collagen deposition, muscularization of arteries, increased SOD levels in the lungs, and decreased the expression of pSTAT-3 and p-MYPT1. Overall, CAR-modified-liposomes of SOD plus fasudil, given every 72 h, was as efficacious as plain drugs, given every 48 h, suggesting that the formulation can reduce the total drug intake, systemic exposures, and dosing frequency.

Indexed as

1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAnimalsArterial PressureChemistry, PharmaceuticalHemodynamicsHypertension, PulmonaryHypertrophy, Right VentricularLiposomesLungMaleMonocrotalineRatsRats, Sprague-Dawleyrho-Associated KinasesSuperoxide DismutaseVasodilator Agents1-(5-Isoquinolinesulfonyl)-2-MethylpiperazinefasudilLiposomesMonocrotalinerho-Associated KinasesSuperoxide DismutaseVasodilator Agentsfasudilinhalationliposomespulmonary arterial hypertensionsuper oxide dismutase

Identifiers

PMID28165252
PMCPMC5814122
OpenAlexW2586530517

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.