{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T08:01:52Z","timestamp":1769587312762,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,1,2]],"date-time":"2014-01-02T00:00:00Z","timestamp":1388620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Factor VIII (FVIII) is an important cofactor in the blood coagulation cascade and its deficiency or dysfunction causes hemophilia A (HA), a bleeding disorder. Replacement with recombinant FVIII is limited by a short half\u2010life and the development of inhibitory antibodies. A phosphatidylinositol (PI) containing lipid nanoparticle was developed that, when associated with FVIII, reduces immunogenicity and prolongs circulation of the therapeutic protein in HA mice. A multiple dose level pharmacokinetic (PK) study of human free FVIII and its FVIII\u2013PI complex over a clinically relevant range of doses (20, 40 and 200\u2009IU\/kg) was conducted in HA mice to investigate linearity of the PK and to determine if the reduced catabolism of FVIII following association with PI particles, previously only observed in the terminal phase following 400\u2009IU\/kg, could be extendable over a range of doses. The findings suggest that the disposition of FVIII is best characterized by a two\u2010compartment model with saturable Michaelis\u2010Menten elimination. Spontaneous complexation of FVIII with PI particles significantly increases plasma survival of the protein at 20 and 40\u2009IU\/kg doses. Human simulations at 40\u2009IU\/kg project an increase in the terminal half\u2010life and the time to reach a minimum therapeutic threshold of 0.01\u2009IU\/ml of 5.4\u2009h and 40\u2009h, respectively, compared with free FVIII. Formulation with PI containing lipid particles may represent a viable delivery strategy for improving FVIII therapy. 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