Cationic amphiphilic peptide-based delivery platforms for negatively charged active pharmaceutical ingredients including short interfering RNA

Peptide sequences have been recently proposed as suitable building blocks for the formulation of supramolecular aggregates that can be used to deliver diagnostic or therapeutic agents.The encapsulation of these active molecules into nanoparticles allows them to overcome some in vivo drawbacks (e.g.degradation, inability to cross barriers). 1Positively charged nanoparticles, such as micelles or polymeric nanoparticles, have been proposed as suitable delivery carriers for RNA-based therapeutics. 2Here we report the preparation of novel peptide based nanovectors as promising delivery systems for short interfering RNA (siRNA).We synthesized a library of eighteen cationic lipopeptides that were explored as charge modifier of peptide gels and nanogels. 3In any case, the presence of a variable number of positive charges were exploited to favor non-covalent electrostatic interactions of model siRNA.