Temperature-Triggered Nanosphere Formation Through Self-Assembly of Amphiphilic Polyphosphazene

Summary: An amphiphilic graft polyphosphazene with a molar ratio of poly(N-isopropylacrylamide) (PNIPAm) to ethyl glycinate (GlyEt) of 0.54:1 was synthesized. This copolymer in aqueous solution exhibited two temperature induced phase transitions at 17.2 and 33.7 °C, which correspond to the transformation of primary aggregate morphology (at Tph1) and the collapse of PNIPAm chains (at Tph2) respectively. Network micelles were assembled in water at lower temperature (far below Tph1), and then narrowly dispersed nanoparticles were formed above Tph1, while inter-nanoparticle aggregation occurred due to the collapse of PNIPAm chains surrounding the GlyEt core when the temperature was above Tph2. Through solubilization of the hydrophobic drug ibuprofen into polymeric aggregates at lower temperature, drug loaded nanospheres were prepared successfully. In vitro release revealed that sustained drug release was achieved with this novel delivery system. These results suggest that this novel copolymer could be used as a potential drug carrier, especially for the delivery of hydrophobic biocompounds through parenteral administration.Schematic illustration of the temperature-triggered self-assembly process of PNIPAm/GlyEt-PPP in aqueous solution.