title: Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier.
abstract: We produced low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as a carrier for heparin-binding growth factors, such as fibroblast growth factor-2 (FGF-2). A mixture of low-molecular-weight heparin (MW: about 5000 Da, 6.4 mg/mL) and protamine (MW: about 3000 Da, 10 mg/mL) at a ratio of 7:3 (vol:vol) yields a dispersion of microparticles (1-6 microm in diameter). In this study, diluted low-molecular-weight heparin solution in saline (0.32 mg/mL) mixed with diluted protamine (0.5 mg/mL) at a ratio at 7:3 (vol:vol) resulted in soluble nanoparticles (112.5 +/- 46.1 nm in diameter). The generated NPs could be then stabilized by adding 2 mg/mL dextran (MW: 178-217 kDa) and remained soluble after lyophilization of dialyzed LMW-H/P NP solution. We then evaluated the capacity of LMW-H/P NPs to protect activity of FGF-2. Interaction between FGF-2 and LMW-H/P NPs substantially prolonged the biological half-life of FGF-2. Furthermore, FGF-2 molecules were protected from inactivation by heat and proteolysis in the presence of LMW-H/P NPs.
authors.affiliation: Research Institute, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Mori
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Satoko
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Kawakami
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Takemi
authors.initials: T
authors.lastname: Matsui
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
mesh_terms: D002478:Cells, Cultured; D003460:Crystallization / Q000379:methods; D004058:Diffusion; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis*; D004339:Drug Compounding / Q000379:methods; D042783:Endothelial Cells / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D008968:Molecular Conformation; D050997:Nanomedicine / Q000379:methods; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011479:Protamines / Q000008:administration & dosage / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D006495:Heparin, Low-Molecular-Weight; D046911:Macromolecular Substances; D011479:Protamines; D016222:Fibroblast Growth Factor 2
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