To demonstrate the relevance of the prodrug approach during this process, a control rROPISA similar to G1 was also carried out but in the presence of free Gem (5 wt %) instead of GemMA. As expected, no Gem was found in the copolymer nanoparticles after purification, as shown by the absence of characteristic Gem proton signals on the 1 H-NMR spectrum (Figure ). This result therefore ruled out potential adsorption of Gem onto the copolymer nanoparticles and the need to establish a chemical linkage between the drug and the copolymer.