Evidence map›Paper›PMID 27372547›Full record

ArticleJournal of pharmaceutical sciences2016

Soy Phosphatidylinositol-Containing Lipid Nanoparticle Prolongs the Plasma Survival and Hemostatic Efficacy of B-domain-Deleted Recombinant Canine Factor VIII in Hemophilia A Dogs.

Krithika A Shetty, Elizabeth P Merricks, Robin Raymer, Natalie Rigsbee, Timothy C Nichols, Sathy V Balu-Iyer

Abstract read
In one paragraph

Article in Journal of pharmaceutical sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 31% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. An Observational Study from Long-Term AAV Re-administration in Two Hemophilia Dogs.Molecular therapy. Methods & clinical development · 2018
    Article
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 2 institutions in 1 country.

Krithika A ShettyDepartment of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York 14214.
Elizabeth P MerricksDepartment of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27516; Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27516.
Robin RaymerDepartment of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27516; Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27516.
Natalie RigsbeeDepartment of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27516; Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27516.
Timothy C NicholsDepartment of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27516; Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27516.
Sathy V Balu-IyerDepartment of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York 14214. Electronic address: svb@buffalo.edu.
University of North Carolina at Chapel Hill · USUniversity at Buffalo, State University of New York · US

Funding

Maintenance of Models of Human Hemophilia and VWDR24HL063098 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI NICHOLS, TIMOTHY CHARLES · 1999 to 2019
$15.1M
HL-Development and Pharmacology of novel lipidic rAHF and biotherapeuticsR01HL070227 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI BALU-IYER, SATHY VENKAT · 2002 to 2019
$5.0M
NHLBI NIH HHS R01 HL070227NHLBI NIH HHS R24 HL063098
6 · The paper itself

Abstract

Soy phosphatidylinositol (PI)-containing lipid nanoparticles prolong plasma survival, improve hemostatic efficacy, and decrease immunogenicity of human B-domain-deleted factor VIII (BDD FVIII) in hemophilia A (HA) mice. We hypothesize that PI-associated BDD FVIII is more potent than the free protein and, using mathematical modeling, have projected that PI-associated BDD FVIII could be used for once-weekly prophylactic dosing in patients. To facilitate translation to the clinic, comparative plasma survival and ex vivo efficacy of PI-associated recombinant canine FVIII (PI-rcFVIII) were evaluated in HA dogs. Two HA dogs were administered a 50-U/kg intravenous dose of free or PI-rcFVIII. rcFVIII activity measurements and ex vivo efficacy analyses such as whole blood clotting time and thromboelastography were conducted on recovered plasma and whole blood samples. PI association decreased clearance (∼25%) and increased plasma exposure (∼1.4-fold) of rcFVIII. PI-rcFVIII-treated animals had prolonged improvements in whole blood clotting time and thromboelastography parameters compared to free rcFVIII-treated animals. Because rcFVIII is a BDD form of FVIII, these studies provide proof of principle that observations with human BDD FVIII in mice translate to higher animal species. In addition, PI-rcFVIII has potential applications in canine HA management and as a bypass therapy in inhibitor-positive HA patients.

Indexed as

AnimalsDogsDrug CarriersDrug CompoundingDrug StabilityFactor VIIIFemaleGlycine maxHemophilia AHemostaticsInjections, IntravenousModels, BiologicalNanoparticlesPhosphatidylinositolsRecombinant ProteinsDrug CarriersFactor VIIIHemostaticsPhosphatidylinositolsrecombinant factor VIII SQRecombinant Proteinsnanoparticlespharmacodynamicspharmacokineticsphospholipidsprotein delivery

Identifiers

PMID27372547
PMCPMC4982397
OpenAlexW2462687223

What OpenQuestion holds

Textmetadata
LicenceTDM
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.