Surface Crosslinked Gelatin Nanoparticles As New Tool for the Delivery of Hydrophilic Macromolecular Drugs

Abstract

For the delivery of hydrophilic macromolecules, a novel flexible, hydrophilic delivery system based on gelatin nanoparticles is developed. Stabilization of gelatin in water is addressed using an apolar zero length crosslinker, i.e., diisopropylcarbodiimide (DIC). Crosslinking of GNPs with polar crosslinkers has certain limitations not only crosslinking gelatin nanoparticles but also the loaded proteins, which interfere not only in the release of cargo but also their biological activity. Therefore, we introduced a novel crosslinking approach termed as interfacial crosslinking with the application of DIC which specifically crosslink the colloidal interface and not diffusing into the interior of nanoparticle. In this context, critical process parameters involved in the crosslinking process have been investigated in order to obtain optimum preparation conditions. The main challenge while formulating these surface crosslinked gelatin nanoparticles (scGNPs) was purification. The centrifugation results in the formation of non redispersible pellet. Therefore, we optimized tangential flow filtration as a promising alternative purification tool. For the final proof of our hypothesis that the hydrophobic crosslinker crosslink only the colloidal interface of GNPs without crosslinking the loaded protein, the surface crosslinked GNPs were loaded with a model hydrophilic protein, i.e., lysozyme. This proved scGNPs as a flexible delivery system for protein based drugs.