Bisphosphonate-coated BSA nanoparticles lack bone targeting after systemic administration.
A polymeric conjugate of polyethyleneimine-graft-poly(ethylene glycol) and 2-(3-mercaptopropylsulfanyl)-ethyl-1,1-bisphosphonic acid (PEI-PEG-thiolBP) was prepared and used for surface coating of bovine serum albumin (BSA) nanoparticles (NPs) designed for bone-specific delivery of bone morphogenetic protein-2 (BMP-2). The NP coating was achieved with a dialysis and an evaporation method, and the obtained NPs were characterized by particle size, zeta-potential, morphology, and cytotoxicity in vitro. The particle size and surface charge of the NPs could be effectively tuned by the PEG and thiolBP substitution ratios of the conjugate, the coating method, and the polymer concentration used for coating. The PEG modification on PEI reduced the toxicity of PEI and the coated NPs, based on in vitro assessment with human C2C12 cells and rat bone marrow stromal cells. On the basis of an alkaline phosphatase (ALP) induction assay, the NP-encapsulated BMP-2 displayed full retention of its bioactivity, except for BMP-2 in PEI-coated NPs. By encapsulating (125)I-labeled BMP-2, the polymer-coated NPs were assessed for hydroxyapatite (HA) affinity; all NP-encapsulated BMP-2 showed significant affinity to HA as compared with free BMP-2 in vitro, and the PEI-PEG-thiolBP coated NPs improved the in vivo retention of BMP-2 compared with uncoated NPs. However, the biodistribution of NPs after intravenous injection in a rat model indicated no beneficial effects of thiolBP-coated NPs for bone targeting. Our results suggested that the BP-conjugated NPs are useful for localized delivery of BMP-2 in bone repair and regeneration, but they are not effective for bone targeting after intravenous administration.
Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada T6G 2G6.
Guilin
G
Wang
Cezary
C
Kucharski
Xiaoyue
X
Lin
Hasan
H
Uludağ
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001842:Bone and Bones / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D004164:Diphosphonates / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D017886:Durapatite / Q000378:metabolism; D005079:Excipients; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000032:analysis / Q000633:toxicity; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000737:chemistry; D051381:Rats; D012710:Serum Albumin, Bovine; D013499:Surface Properties; D014018:Tissue Distribution
D055396:Bone Morphogenetic Protein 2; D004164:Diphosphonates; D004337:Drug Carriers; D005079:Excipients; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D017886:Durapatite