title: Modulated release of OP-1 and enhanced preosteoblast differentiation using a core-shell nanoparticulate system.
abstract: A release-controlled OP-1 delivery system consisting of a suspension of core-shell nanoparticles was prepared. The nanoparticles were composed of a core of positively-charged large unilamellar liposomes and a shell constructed through the L-b-L assembly of alternating layers of negatively-charged sodium alginate and positively-charged chitosan. Cytotoxicity was assayed with MC3T3-E1.4 mouse preosteoblast cells and cell viability was determined by colorimetry (CellQuanti-MTT kit). The system was loaded with a range of OP-1 concentrations and the release profiles were obtained and fitted into the Higuchi model to determine release kinetics. Alkaline phosphatase (ALP) activity of preosteoblasts was evaluated using a micro-BCA assay. The resulting monodisperse and nontoxic spherical nanoparticles exhibited high physical stability in simulated physiological media as well as an extended shelf-life allowing for immediate protein loading before future administration. ALP activity increased over time with the OP-1 loaded delivery system when compared with control, protein alone, and nanoparticles alone (p < 0.05). The system offers copious compartments for protein entrapment including the aqueous core and within the polyelectrolyte layers in the shell and demonstrates a sustained triphasic linear release of OP-1 over a prolonged period of 45 days, in vitro. This system offers a great advantage for optimum growth factor performance when applied in different anatomical sites of varying defect sizes and vascularity.
authors.affiliation: Faculty of Dentistry, McGill University, Montréal (Québec), Canada.
authors.forename: Ziyad S
authors.initials: ZS
authors.lastname: Haidar
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Azari
authors.forename: Reggie C
authors.initials: RC
authors.lastname: Hamdy
authors.forename: Maryam
authors.initials: M
authors.lastname: Tabrizian
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage*; D002454:Cell Differentiation; D002470:Cell Survival; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010006:Osteoblasts / Q000166:cytology*; D010316:Particle Size; D011506:Proteins / Q000737:chemistry
chemical_list: D055419:Bone Morphogenetic Protein 7; D004337:Drug Carriers; D011506:Proteins; D000469:Alkaline Phosphatase