Nanoparticles formed from PNIPAM-g-PEO copolymers in the presence of indomethacin

Biocompatible double-hydrophilic PNIPAM-g-PEO copolymers containing 0.3-3.2 mol% PEO grafts were synthesized and utilized to prepare indomethacin (IMC)-loaded core-shell nanoparticles by dialysis and nanoprecipitation methods. IMC loading was conducted at room temperature using the organic solvents ethanol and DMF, which induced phase separation in the copolymers aqueous solutions due to the cononsolvency of PNIPAM. In ethanol-water solutions, the cononsolvency-induced phase separation of the copolymers promoted effective drug incorporation into the formed micellar structures. In DMF-water system, the formation of the nanoparticles did not correspond to the cononsolvent region of PNIPAM-g-PEO. In this case, hydrophobic interactions between PNIPAM and IMC allowed the copolymer self-association and drug loading. Irrespective of the solvents or preparation methods applied, the drug loading content (DLC) depended on the drug-to-copolymer feed weight ratio. DLC was relatively low at the 0.5:1 ratio but it significantly increased at the ratios of 0.75:1 and 1:1 (DLC approximately 90%). The particle size was strongly affected by the different mechanisms of nanoparticles formation. The nanoprecipitation from ethanol produced significantly smaller particles (<150 nm) with narrow size distribution than the dialysis from DMF. The velocity of indomethacin release from the nanoparticles was influenced by the amount of encapsulated drug, the process being faster at lower DLC.