Nanoparticles based on naturally-occurring biopolymers, most of them endogenous macromolecules, were designed as a versatile generation of delivery platforms for delicate bioactive molecules. The design of these nanosystems was specifically based on our recent finding about the ability of endogenous polyamine spermine (SPM) to interact with anionic biopolymers (ABs) generating ionically cross-linked nanosystems.The initial first generation of these delivery platforms, based on glycosaminoglycans and other polysaccharides, showed a very high association capacity for some delicate bioactive proteins such as growth factors, but a limited capacity to associate negatively charged molecules, such as pDNA and siRNA. However, the versatility of these nanosystems in terms of composition allowed us to customise the association of active ingredients and their physicochemical characteristics. Concretely, we prepared and incorporated gelatine cationized with spermine (CGsp) to their composition. The resulting modified formulations were characterised by a nanometric size (150–340nm) and offer the possibility to modulate their zeta potential (from −35 to 28mV), providing an efficient association of nucleic acids. The biological evaluation of these optimised nanosystems revealed that they are able to be internalised in vivo into corneal and conjunctival tissues and also to provide a significant siRNA gene silencing effect.