Efficient One-Pot Synthesis of Carboxymethyl Chitosan Hydrogel for Sustained Release of Ibuprofen and Sulfadiazine

Herein, we report an efficient one-pot strategy to prepare a carboxymethyl chitosan (CMCh) hydrogel capable of releasing small drugs like ibuprofen (Ibu) and sulfadiazine (Sfd) in a prolonged manner. The drug-loaded CMCh hydrogels are synthesized simply by adding ethylene glycol diglycidyl ether (EGDE) into a CMCh/poly(vinyl alcohol) (PVA)/zinc acetate/drug solution at room temperature and then heating the mixture at T = 60 °C for 4 h. EGDE is employed not only to cross-link the CMCh and PVA chains but also to immobilize the drugs onto the hydrogel matrix via epoxy-acid and/or epoxy-amino chemistry. The resultant hydrogels exhibit a three-dimensional interconnected macroporous architecture, as revealed by scanning electron microscope measurements. Swelling and compression tests indicate that the addition of 1.25% PVA leads to relatively good stability in phosphate buffered saline (PBS) and an improved compressive strength of 38.9 Kpa. At last, in vitro drug release studies are performed in PBS buffer at T = 37 °C, showing that an optimized CMCh hydrogel allows for a sustained release of Ibu over 21 days and Sfd for 49 days, respectively. Different drug release mechanisms for Ibu- and Sfd-loaded CMCh hydrogels are discussed after fitting the release kinetic data to five classical mathematical models.