Evidence map›Paper›PMID 17705286›Full record

ArticleJournal of pharmaceutical sciences2008

Phosphatidylserine containing liposomes reduce immunogenicity of recombinant human factor VIII (rFVIII) in a murine model of hemophilia A.

Karthik Ramani, Razvan D Miclea, Vivek S Purohit, Donald E Mager, Robert M Straubinger, Sathy V Balu-Iyer

Open access · greenAbstract read
In one paragraph

Article in Journal of pharmaceutical sciences, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

39 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Immunogenicity of Protein Pharmaceuticals.Journal of pharmaceutical sciences · 2019
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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.

Karthik RamaniDepartment of Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, New York 14260, USA.
Razvan D Miclea
Vivek S Purohit
Donald E Mager
Robert M Straubinger
Sathy V Balu-Iyer
University at Buffalo, State University of New York · USRoswell Park Comprehensive Cancer Center · US

Funding

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 R01 HL-70227PHS HHS S10-013665
6 · The paper itself

Abstract

Factor VIII (FVIII) is a multidomain protein that is deficient in hemophilia A, a clinically important bleeding disorder. Replacement therapy using recombinant human FVIII (rFVIII) is the main therapy. However, approximately 15-30% of patients develop inhibitory antibodies that neutralize rFVIII activity. Antibodies to epitopes in C2 domain, which is involved in FVIII binding to phospholipids, are highly prevalent. Here, we investigated the effect of phosphatidylserine (PS)-containing liposomes, which bind to C2 domain with high affinity and specificity, upon the immunogenicity of rFVIII. Circular dichroism studies showed that PS-containing liposomes interfered with aggregation of rFVIII. Immunogenicity of free- versus liposomal-rFVIII was evaluated in a murine model of hemophilia A. Animals treated with s.c. injections of liposomal-rFVIII had lower total- and inhibitory titers, compared to animals treated with rFVIII alone. Antigen processing by proteolytic enzymes was reduced in the presence of liposomes. Animals treated with s.c. injections of liposomal-rFVIII showed a significant increase in rFVIII plasma concentration compared to animals that received rFVIII alone. Based on these studies, we hypothesize that specific molecular interactions between PS-containing bilayers and rFVIII may provide a basis for designing lipidic complexes that improve the stability, reduce the immunogenicity of rFVIII formulations, and permit administration by s.c. route.

Indexed as

AnimalsBiological AvailabilityFactor VIIIFemaleHemophilia ALiposomesMaleMicePhosphatidylserinesRecombinant ProteinsF8 protein, humanFactor VIIILiposomesPhosphatidylserinesRecombinant Proteins

Identifiers

PMID17705286
PMCPMC2574438
OpenAlexW1971342115

What OpenQuestion holds

Textmetadata
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.