Hyaluronic acid-g-PPG and PEG-PPG-PEG hybrid thermogel for prolonged gel stability and sustained drug release

Hyaluronic acid-graft-poly(propylene glycol) (HA-g-PPG) was prepared to induce hydrophobic interactions between HA-g-PPG and F127 PPGs (poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol)) and consequent increases in gel stability of F127 gel. Molecular weights of 340, 1000, and 2500 Da were used for PPG, and grafting ratios of HA-g-PPG varied over 3%, 12%, and 50%. Using rheology measurements, 1H NMR spectra, lower critical solution temperature measurements, dynamic light scattering, and transmission electron spectroscopy, hydrophobic crosslinking and intermicellar bridge formation were suggested in the aqueous HA-g-PPG/F127 hybrid solutions. In particular, the gel stability of the HA-g-PPG/F127 hybrid thermogel increased from 2 days (F127 only) to 6 days, thus the hybrid thermogel can provide longer delivery of an incorporated drug. The HA-g-PPG/F127 thermogel exhibited tissue compatibility in the subcutaneous layer of rats. The protein drug release from the gel indicated that interactions between negative charged HA-g-PPG and positive charged drug (calcitonin) reduced initial burst release.