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. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009