Novel core-shell nanocaspules for localized growth factor delivery

Objective: This work is to develop a biocompatible growth factor delivery system which would promote the viability and release of proteins so that to optimize de novo bone regeneration in mandibular distraction osteogenesis (MDO). Design: A liposomal core incorporated in a shell of alternating L-b-L (Layer-by-Layer) self-assembled natural polyelectrolytes; alginate and chitosan. Methods: The L-b-L build-up, morphological analysis, in vitro characterization and physical stability over time and post-lyophilization and rehydration were optimized. The loading capacity (LC), encapsulation efficiency (EE) and release profile of the delivery system were quantified using a model protein, bovine serum albumin (BSA) over an extended period of 30 days. Results: The L-b-L deposition technique proved successful in building hydrophilic, non-toxic, spherical and stable cationic particles < 400 nm in size. Our results showed that by increasing the number of polymer layers onto the liposomal core, the LC and EE of the delivery system are markedly enhanced. Controlled, biphasic, linear and sustained release of BSA was observed throughout the study with up to 88% of BSA released over 4 weeks before reaching a plateau, thus the core-shell effect is demonstrated. Conclusion: This system has the following interesting features: (i) rapid and mild formulating conditions; (ii) nanosized and biocompatible; (iii) good LC and EE; and (iv) provides continuous release over extended periods of time. Hence, it is a promising and cost-effective carrier for the local administration of therapeutic growth factors. Ongoing work aims at optimizing the system with a bone morphogenetic protein; BMP-7, in vitro as well as in a rabbit model of MDO.