4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Effect of biophysical properties of Phosphatidylserine (PS) particle on immune tolerance induction towards Factor VIII in a Hemophilia A mouse model

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          A major complication in the replacement therapy of Factor FVIII (FVIII) for Hemophilia A (HA) is the development of unwanted immune responses. Previous studies from our lab have shown that pretreatment of FVIII in the presence of Phosphatidylserine (PS) resulted in hyporesponsiveness to subsequent administration of FVIII alone, due to the ability of PS to convert an immunogen to a tolerogen. We investigated the importance of biophysical properties of PS liposomes on its ability to convert an immunogen to a tolerogen. PS particles were prepared differing in size, protein-lipid topology, lamellarity and % association to FVIII keeping the composition of the particle same. PS particles were prepared in two different sizes with differing biophysical properties, smaller particles in the nanometer range (200 nm) and larger size particles in the micron range (2um). HA animals treated with both the nanometer and micron size PS particle showed a significant reduction in anti-FVIII antibody titers when compared to animals receiving free FVIII alone. Upon rechallenge with free FVIII animals that received FVIII along with the nanometer size particle continued to show reduced antibody responses. Animals receiving the micron size particle showed a slight increase in titers although they remained significantly lower than the free FVIII treated group. Upon culture with bone marrow dendritic cells (BMDCs), the nanometer size particle showed a reduction in CD40 expression and an increase in TGF-β cytokine production; which was not observed with the micron size particle. These results show that biophysical properties of PS play an important role in tolerance.

          Related collections

          Author and article information

          Journal
          2985195R
          5156
          J Pharm Sci
          J Pharm Sci
          Journal of pharmaceutical sciences
          0022-3549
          1520-6017
          23 June 2016
          16 July 2016
          October 2016
          01 October 2017
          : 105
          : 10
          : 3039-3045
          Affiliations
          Department of Pharmaceutical Sciences
          Author notes
          [* ]Corresponding author: 359 Kapoor Hall, University at Buffalo, The State University of New York, Buffalo, New York 14215, Telephone: (716)-645-4836, Fax: (716)-645-3693, svb@ 123456buffalo.edu
          [†]

          Formerly Sathyamangalam V. Balasubramanian

          Article
          PMC5021571 PMC5021571 5021571 nihpa797036
          10.1016/j.xphs.2016.06.008
          5021571
          27431011
          Categories
          Article

          Comments

          Comment on this article