title: Polyethylenimine-PEG coated albumin nanoparticles for BMP-2 delivery.
abstract: Bone Morphogenetic Protein-2 (BMP-2) plays an important role in stimulating new bone formation, and has been utilized in clinical bone repair by implantation. In this study, we report a nanoparticulate (NP) system for BMP-2 delivery based on bovine serum albumin (BSA) NPs stabilized with a poly(ethylene glycol) modified polyethylenimine (PEI-PEG) coating. PEI-PEG with different PEG substitutions were synthesized, and the cell viability assay showed PEG substitution greatly reduced the cytotoxicity of the native PEI. Furthermore, PEI-PEG coated BSA NPs demonstrated smaller size and decreased zeta potential compared to PEI-coated NPs. The bioactivity of the encapsulated BMP-2 and the toxicity of PEI-PEG coated NPs were examined by the alkaline phosphatase (ALP) induction assay and the MTT assay, respectively, using human C2C12 cells. The results indicated that BMP-2 remained bioactive in NPs and PEI-PEG coating was advantageous in reducing the NP toxicity as compared to PEI. A 7-day pharmacokinetics study showed the BMP-2 retention in PEI-PEG coated NPs was similar to the uncoated NPs, but lower than that of the PEI-coated NPs. The osteoinductivity of BMP-2 delivered in NPs was determined by subcutaneous implantation in rats, and the results revealed that PEI-PEG coated BSA NPs induced significant de novo bone formation after implantation, while PEI-coated NPs demonstrated much less bone formation. We conclude that BMP-2 delivered by PEGylated PEI-coated BSA NPs displays favorable biocompatibility and promotes new bone formation after implantation.
authors.affiliation: Department of Chemical and Materials Engineering, University of Alberta, Canada.
authors.forename: Sufeng
authors.initials: S
authors.lastname: Zhang
authors.forename: Cezary
authors.initials: C
authors.lastname: Kucharski
authors.forename: Michael R
authors.initials: MR
authors.lastname: Doschak
authors.forename: Walter
authors.initials: W
authors.lastname: Sebald
authors.forename: Hasan
authors.initials: H
authors.lastname: Uludağ
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D012709:Serum Albumin; D011092:Polyethylene Glycols; D011094:Polyethyleneimine