Thermosensitive nanocarriers for drug delivery from polyelectrolyte complexes of hyaluronic acid grafted with PEO PPO: old polymers, new combination

Abstract

International audienceColloidal polyelectrolyte complexes (PECs) from hyaluronic acid (HA) have received increasing attention recently as simple-to-prepare but highly robust drug delivery systems (DDS) with the advantages of nanomedicine, green chemistry and the inherent properties of HA, i.e. excellent biocompatibility, biodegradability and selective biological interactions. Meanwhile, poly(ethylene oxide)-co-poly(propylene oxide) (PEO-PPO) is a classical thermosensitive copolymer widely employed in thermoresponsive biomedical materials. Despite the well-known advantages of these polymers, there has so far been no nanoparticulate DDS reported from PEO-PPO-grafted HA. In our work, a novel type of hybrid nanoparticulate system has been developed from PECs of HA grafted with Jeffamine® M-2005 (M2005), a commercialized amine-terminated PEO-PPO, electrostatically complexed with diethylaminoethyl dextran (DEAE-D) or poly-L-lysine (PLL), which are common polycations in biomedical fields. It was revealed that the presence of M2005 grafts as well as their thermoresponsiveness leads to a series of interesting properties of PEC nanocarriers, including high stability against physiological salinity, thermo-controllable drug encapsulation, thermo-triggered drug release, better-preserved particle size after lyophilization, and transformability into more compact and long-term stable polymeric nanoparticles using autoclave. PLL was also found to be more beneficial than DEAE-D in terms of particle stability and drug encapsulation, rendering HA-M2005/PLL PECs the most promising among the investigated systems. These findings not only provide a better insight into the physicochemical properties of PECs but also highlight the potential of thermoresponsive PECs based on PEO-PPO-grafted HA as a very new concept of hybrid material from already well-known polymers for drug delivery