Chitosan-reinforced PHB hydrogel and aerogel monoliths fabricated by phase separation with the solvent-exchange method

The poly(3-hydroxybutyrate) (PHB) organogel monoliths were prepared by nonsolvent-induced phase separation (NIPS). The NIPS-derived organogels were solvent-exchanged with chitosan (CS) solution, resulting in the successful loading of CS into PHB hydrogel. With increasing the CS content, the as-prepared composite hydrogels became syringe injectable with excellent thixotropy due to the increase in the gel network's hydrophilicity. The hydrogels were successfully freeze-dried into PHB/CS composite aerogels, which exhibited remarkably improved compressive modulus/collapse strength of 1.6 MPa/159 kPa compared to 0.5 MPa/31 kPa for pure PHB aerogels. The effect of CS on gel crystallization and structure was also investigated. The amphiphilic PHB/CS hydrogels effectively entrapped both hydrophilic/cationic doxorubicin (DOX) and hydrophobic/anionic indomethacin (IDM). The drug release behavior depended on the charge interactions between drugs and CS. The accelerated DOX release in acidic condition from injected hydrogels owing to the charge repulsion shows potential for a controlled and localized cancer therapy.