Supramolecular self-assembly and controllable drug release of thermosensitive hyperbranched multiarm copolymers

A novel temperature-responsive hyperbranched multiarm copolymer with a hydrophobic hyperbranched poly(3-ethyl-3-(hydroxymethyl) oxetane) (HBPO) core and thermosensitive poly(N-isopropylacrylamide) (PNIPAM) arms was synthesized via the atom transfer radical polymerization (ATRP) of NIPAM monomers from a hyperbranched HBPO macroinitiator. It was found that HBPO-star-PNIPAM self-assembled into multimolecular micelles (around 60 nm) in water at room temperature according to pyrene probe fluorescence spectrometry, 1H NMR, TEM, and DLS measurements. The micelle solution showed a reversible thermosensitive phase transition at a lower critical solution temperature (LCST) (around 32°C) observed by variable temperature optical absorbance measurements. Variable temperature NMR and DLS analyses demonstrated that the LCST transition originated from the secondary aggregation of the micelles driven by increasing hydrophobic interaction due to the dehydration of PNIPAM shells upon heating. The drug loading and release properties of HBPO-star-PNIPAM micelles were also investigated using prednisone acetate as a model drug. The micelles showed a much improved drug encapsulation efficiency and temperature-dependent sustainable release behavior due to the special micellar structure. The micelles exhibited no apparent cytotoxicity against human HeLa cells.