title: Pharmacokinetics and bone formation by BMP-2 entrapped in polyethylenimine-coated albumin nanoparticles.
abstract: The osteoinductive growth factor, bone morphogenetic protein-2 (BMP-2), is capable of inducing de novo bone formation after implantation. A nanoparticulate (NP) system was developed for BMP-2 delivery based on NPs fabricated from bovine serum albumin (BSA) and stabilized by polyethylenimine (PEI) coating. In this study, the pharmacokinetics and osteoinductivity of BMP-2 delivered with different BSA NP formulations were determined by subcutaneous implantation in rats. A 7-day pharmacokinetics study showed that PEI coating on NPs effectively reduced the initial burst release of BMP-2 and prolonged the BMP-2 retention at implantation site. However, the uncoated BMP-2 NPs (BMP-2 loading of 1.44% w/w) were able to induce a robust ectopic bone formation, while no bone formation was found by the BMP-2 NPs coated with PEI. The toxicity of the PEI used for NP coating was determined to be the reason for lack of osteoinduction. Increasing BMP-2 loading (up to 5.76% w/w) was then employed to formulate NPs with lower PEI content; the higher BMP-2 loading was found to better promote induction of de novo bone. Our findings indicated that PEI coating on BSA NPs was effective for controlling BMP-2 release from NPs, but the toxicity of cationic PEI was a concern for the osteoinductive activity, which should be alleviated by further optimization of NP formulations.
authors.affiliation: Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada.
authors.forename: Sufeng
authors.initials: S
authors.lastname: Zhang
authors.forename: Michael R
authors.initials: MR
authors.lastname: Doschak
authors.forename: Hasan
authors.initials: H
authors.lastname: Uludağ
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002417:Cattle; D002460:Cell Line; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010012:Osteogenesis; D011094:Polyethyleneimine / Q000737:chemistry*; D019736:Prostheses and Implants; D051381:Rats; D012710:Serum Albumin, Bovine / Q000737:chemistry*
chemical_list: D055396:Bone Morphogenetic Protein 2; D012710:Serum Albumin, Bovine; D011094:Polyethyleneimine