In vitro and in vivo biocompatibility study of a hybrid nanoparticulate BMP-7/OP-1 delivery system

A hybrid, nanosized, localized and release-controlled bone morphogenetic protein delivery system consisting of a Iiposomal core incorporated into a shell of alternating layer-by-layer self-assembled natural polyelectrolytes has been formulated. Hydrophilic, monodisperse, spherical and stable cationic nanoparticles with an extended shelf-life allowing immediate protein loading prior to clinical administration resulted. In this study, the potential in vitro and in vivo cytotoxicity of unloaded and loaded nanoparticles with bone morphogenetic porotein-7 (also known as osteogenic protein-1 or OP-1) were investigated. In vitro cytotoxicity was assayed with MC3T3-E1.4 mouse preosteoblast cells and cell viability was determined by colorimetry (CeIlQuanti-MTT™kit). A total of 22 young male normal Wistar rats were injected intramuscularly and monitored over a period of 14 weeks for any signs of inflammation and/or adverse reactions. Blood samples (600 μL per collection) were withdrawn on days 0 (baseline: pre-injection) and post-injections on days 1, 7, 14, 28 and 56. Hematological and biochemical analysis followed. Body weight changes over the treatment period were noted as well. Overall, all animals showed no obvious toxic health effects, immune responses and/or change in organ functions. Hence, a safe and promising nanosized carrier for the administration of therapeutic growth factors is presented.