Mechanical properties of gelatin nanoparticles in dependency of crosslinking time and storage.

Mechanical properties of nanoparticles are an important characteristic for drug delivery and therefore, they have gained interest in pharmaceutical research during the last years. Among others, cellular uptake, blood circulation time and accumulation in organs are influenced by the elastic modulus of nanoparticles. Thus, by varying the stiffness of nanoparticles a more specific drug targeting might be achieved. Gelatin nanoparticles (GNPs) show advantageous characteristics in respect to encapsulation and delivery of hydrophilic drugs such as antibodies or other biologicals. Furthermore, the GNPs as hydrogel-nanoparticles offer adjustable elastic behavior. In this study, a method for GNP sample preparation and the determination of the mechanical properties by nanoindentation experiments using atomic force microscopy (AFM) was developed. The obtained force-distance curves were evaluated and fitted with the Hertzian model in order to calculate the Young's modulus. GNPs were crosslinked with glutaraldehyde (GTA) for different incubation times to investigate a possible modification of the Young's modulus. In addition, this study addresses the influence of storage on the mechanical characteristics of GNPs. The results provide first insights about the elastic properties of GNPs and their development over time. In the tested range of crosslinking times no notable differences in the mechanical properties occurred. In turn, the influence of the storage on the mechanical particle properties was observed: particle stiffness raised over time. Furthermore, it could be observed that the cellular uptake in a model cell line (A549) was increased for harder particles.