Small hydrophilic drugs are widely used for systemic administration, but they suffer from poor absorption and fast clearance. Their nanoencapsulation can improve biodistribution, targeted delivery, and pharmaceutical efficacy. Hydrophilics are effectively encapsulated in compartmented particles, such as liposomes or extracellular vesicles, which are biocompatible but poorly customizable. Polymeric vectors can form compartmental structures, also being functionalizable. Here, we report a system composed of polymeric stabilized reversed micelles for hydrophilic drugs encapsulation. We optimized the preparation procedure, and calculated the critical micellar concentration. Then, we developed a strategy for stabilization that improves micelle stability upon dilution. We tested the drug loading and delivery capabilities with creatine as a drug molecule. Prepared stabilized reversed micelles had a size of around 130 nm and a negative z-potential around -16 mV, making them functional as a drug carrier. The creatine cargo increased micelle size and depended on the loading conditions. The higher amount of loaded creatine was around 60 μg/mg of particles. Delivery tests indicated full release within three days in micelles with the lower cargo, while higher loadings can provide a sustained release for longer times. Obtained results are interesting and encouraging to test the same system with different drug cargoes.
Keywords: amphiphilic copolymers; crosslinking; hydrophilic cargo; reversed micelles.