OP-1 loaded core-shell nanoparticles: cytotoxicity, osteogenic activity and release kinetics

Objective: This work is to develop a release-controlled bone morphogenetic protein-7 (BMP-7, also known as osteogenic protein 1 or OP-1) delivery system that would optimize de novo bone tissue regeneration and accelerate the consolidation phase in mandibular distraction osteogenesis (MDO). Methods: A suspension of core-shell nanoparticles was prepared via the L-b-L (Layer-by-Layer) self-assembly of natural polyelectrolytes; alginate and chitosan on nanoscaled liposomes. Cytotoxicity was assayed with MC3T3- E1.4 mouse pre-osteoblast cells and cell viability was determined by colorimetry. The system was loaded with OP-1 and the release profiles were obtained and fitted into the Higuchi model for release kinetics. Alkaline phosphatase (ALP) activity in pre-osteoblasts was determined with respect to the release of ñ-nitrophenol from ñ-nitrophenylphosphate substrate. Results: The resulting monodisperse and non-toxic spherical nanoparticles exhibited high physical stability in simulated physiological media as well as an extended shelf-life allowing immediate protein loading prior to administration. ALP activity increased over time with the OP-1 loaded delivery system when compared to controls (ñ<0.05). The system offers copious compartments for protein entrapment including the aqueous core and within the polyelectrolyte shell demonstrating a sustained tri-phasic linear release of OP-1 over a prolonged period of 45 days, in vitro. Conclusion: This system is a promising and cost-effective carrier for the local administration of therapeutic growth factors. Ongoing work aims at optimizing the system in a rabbit model of MDO.