Delivery of Flt3 ligand (Flt3L) using a poloxamer-based formulation increases biological activity in mice

S. N. Robinson, J. M. Chavez, V. M. Pisarev, R Lee Mosley, G. J. Rosenthal, J. M. Blonder, James E Talmadge

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Fms-like tyrosine kinase (Flt3L) is a potent stimulator of hematopoietic progenitor cell (HPC) expansion and mobilization; however, this requires 7-10 days of administration. We investigated whether sustained delivery of Flt3L using a poloxamer-based matrix (PG) could accelerate and/or improve the hematopoietic activity of Flt3L in mice. A single injection of PG-Flt3L stimulated significantly more rapid and greater HPC mobilization to the spleen and peripheral blood than the daily injection of Flt3L formulated in saline. Pharmacokinetic analysis demonstrated that the formulation of Flt3L in PG prolonged its elimination (Tβ) half-life (2.3-fold) and increased its bioavailability (>two fold) and the time to maximum serum concentration (Tmax) (2.7-fold). Further, coadministration of G-CSF and PG-Flt3L allowed lower doses of Flt3L to be active, with significantly greater hematopoietic and mobilization activity, compared to the same total dose of G-CSF, Flt3L or G-CSF and Flt3L formulated in saline. These data demonstrate that formulation of Flt3L in PG significantly accelerates and increases HPC expansion and mobilization. The observation of increased bioactivity by PG-Flt3L in rodents suggests the potential for improved clinical efficacy of Flt3L by reducing the time required for HPC mobilization.

Original languageEnglish (US)
Pages (from-to)361-369
Number of pages9
JournalBone marrow transplantation
Volume31
Issue number5
DOIs
StatePublished - Mar 1 2003

Fingerprint

Poloxamer
Hematopoietic Stem Cells
Granulocyte Colony-Stimulating Factor
flt3 ligand protein
Vascular Endothelial Growth Factor Receptor-1
Injections
Biological Availability
Half-Life
Rodentia

Keywords

  • Flt3 ligand (Flt3L)
  • Hematopoiesis
  • Mobilization
  • Sustained delivery poloxamer-based matrix

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Delivery of Flt3 ligand (Flt3L) using a poloxamer-based formulation increases biological activity in mice. / Robinson, S. N.; Chavez, J. M.; Pisarev, V. M.; Mosley, R Lee; Rosenthal, G. J.; Blonder, J. M.; Talmadge, James E.

In: Bone marrow transplantation, Vol. 31, No. 5, 01.03.2003, p. 361-369.

Research output: Contribution to journalReview article

Robinson, S. N. ; Chavez, J. M. ; Pisarev, V. M. ; Mosley, R Lee ; Rosenthal, G. J. ; Blonder, J. M. ; Talmadge, James E. / Delivery of Flt3 ligand (Flt3L) using a poloxamer-based formulation increases biological activity in mice. In: Bone marrow transplantation. 2003 ; Vol. 31, No. 5. pp. 361-369.
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