New mild and specific chemical strategies have been developed recently for the selective coupling of biological macromolecules. Among them, the hydrazone ligation strategy offers high chemoselectivity and versatility. We intended to use hydrazone ligation to target the controlled release of therapeutic agents by biological vectors (multilamellar vesicles called onion vectors). An accurate measure of ligation bond stability was needed to ensure that the ligation bond would stand long exposures to physiological conditions. In this study, we have completed a kinetic and thermodynamic characterization of hydrazone formation on a model reaction. The mechanism of the reaction in solution as well as in different self-organized systems (micelles, liposomes and multilamellar vesicles) was investigated. In solution, submicromolar stability was achieved as well as half-lives of several weeks. The kinetics and stability were both enhanced in colloidal media thanks to autoassociation effects. The results were expanded to the realistic case of RGD-peptide coupling to onion vectors. The RGD grafted onion vectors were then tested for their ability to bind endothelial cells in vitro.