title: Hematopoietic progenitor cell mobilization in mice by sustained delivery of granulocyte colony-stimulating factor.
abstract: The objective of these studies was to determine the effect of sustained delivery of growth factors (GFs) on hematopoietic progenitor cells (HPCs) in mice. In these studies, granulocyte colony-stimulating factor (G-CSF) was administered using the poloxamer-based matrix, ProGelz (PG) and G-CSF, and pharmacokinetics (PKs) and HPC mobilization was assessed. A single injection of G-CSF formulated in PG (17% poloxamer-407 and 5% hydroxypropyl methylcellulose [HPMC]) administered to BALB/c mice mobilized HPC significantly more rapidly to the spleen, but not the blood, than multiple injections of saline-formulated G-CSF. Two days after a single injection of PG G-CSF, the frequency of colony-forming unit-culture (CFU-c) in the spleen was increased 289-fold compared with an 8-fold increase after 2 days of twice-daily injections of saline-formulated G-CSF. Indeed, 4 days of twice-daily G-CSF injections were required to achieve the same level of HPC mobilization. In contrast, a similar mobilization of HPC to the blood was observed between PG and saline-formulated G-CSF. The mechanism for the accelerated and increased mobilization to the spleen by the PG-formulation of G-CSF is due, in part, to its increased bioavailability (>1.5-fold), T(max) (6-fold), and prolonged elimination (Tbeta) half-life (>3-fold) as compared with a saline formulation. In addition, we observed a more rapid trafficking of the PG G-CSF to the marrow, which could also facilitate mobilization.
authors.affiliation: MD Anderson, Texas Medical Center, Houston, TX 77030, USA.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Robinson
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Chavez
authors.forename: Joan M
authors.initials: JM
authors.lastname: Blonder
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Pisarev
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.forename: Hongxun
authors.initials: H
authors.lastname: Sang
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Rosenthal
authors.forename: James E
authors.initials: JE
authors.lastname: Talmadge
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D005260:Female; D005269:Femur / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D051379:Mice; D008807:Mice, Inbred BALB C; D012965:Sodium Chloride; D013154:Spleen / Q000187:drug effects
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D012965:Sodium Chloride