Micro- and nanoparticles are designed to deliver drugs and contrast agents to their target site in a controlled manner. One of the greatest obstacles in the performance of such delivery vehicles is their stability in the presence of serum. Here we investigate a method to stabilize a class of liposomes in which lipid vesicles are modified post- fabrication through surface adsorption and anchoring. We hypothesized that the sequential adsorption of functional units followed by covalent cross-linking of the liposome would provide enhanced stability in the presence of human serum. To investigate this hypothesis, liposomes composed of diyne-containing lipids were assembled and functionalized via chitosan conjugated with a hydrophobic anchor and the magnetic resonance (MR) contrast agent, gadolinium, as a model functionality. This strategy served to stabilize the thermodynamically favorable association between liposome and modified functional chitosan. Furthermore, the chitosan-coated, cross-linked liposomes proved more effective as delivery vehicles of MR contrast agents than uncross-linked liposomes due to the reduced liposome degradation and chitosan desorption. Overall, this study demonstrates a useful method to stabilize a broad class of particles used for systemic delivery of various molecular cargos
