Stabilized Reversed Polymeric Micelles as Nanovector for Hydrophilic Compounds

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 mu g/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.

Automated summary

Small hydrophilic drugs are commonly used in systemic administration but have limitations due to poor absorption and fast clearance. Nanoencapsulation of these drugs in compartmented particles, such as liposomes or extracellular vesicles, can enhance their biodistribution, targeted delivery, and pharmaceutical efficacy. In this study, we developed polymeric stabilized reversed micelles as a system for encapsulating hydrophilic drugs. The optimized preparation procedure and stabilization strategy improved the stability of the micelles. These micelles showed potential as drug carriers, with the ability to load and deliver creatine. The results suggest that this system can be further explored for different drug cargoes.