(OP 31) Bioerodible Polymeric Nanoconstructs for the Administration of Hydrophobic Bioactive Agents in Tissue Engineering

Successful tissue regeneration cannot always be achieved by the combination of cells and their scaffold alone. In this cases growth factor or differentiating agents to promote tissues regeneration are required. The goal of this work was to investigate the use of bioerodible nanoparticles as carrier of retinoic acid (RA), which is known to induce differentiation of several cell lines into neurons. Due to its high hydrophobicity and short half-lives in blood, RA parenteral administration is very difficult and oral formulations are characterized by uncertain drug bioavailability. An organic solvent-free method, called "Colloidal-Coating," has been developed for the preparation of nanoparticles based on a copolymer of maleic anhydride and butyl vinyl ether (VAM41) loaded with RA. This method presents numerous advantages if compared with other nanoparticles preparation methods: does not entail the utilization of toxic organic solvents, allows for the preparation of small nanoparticles with narrow size distribution, it is easy to perform, it is based on a reversible process which avoid wastes of material in case of accidental errors during the preparation. The activity of the encapsulated RA was evaluated on SK-N-SH human neuroblastoma cells which are known to undergo inhibition of proliferation and neuronal differentiation upon treatment with RA. The activity RA was not affected by the encapsulation and purification processes. Growth inhibitory effects and morphologic differentiation into neuronal cell was observed indicating the suitability of the developed formulation for neuronal regeneration purposes.