Dual ionically crosslinked chitosan-based injectable hydrogel as drug delivery system

Thermosensitive hydrogels based on chitosan play an important role in the field of tissue engineering and drug delivery system, with excellent properties such as biocompatible, biodegradable, and minimally invasive. In this work, a dual ionically crosslinked injectable hydrogel was composed of polyelectrolyte complex (PEC) and sodium hydrogen carbonate (SHC) as non-toxic gel agent. The PEC was prepared by ionic interaction between positively charged chitosan and negatively charged thermosensitive polymer poly(NIPAm-co-AMPS). The injectable hydrogel with rapid gelation was obtained by optimizing feed ratio, SHC amount, concentration, and temperature. The swelling, temperature sensitive, rheological, and cytotoxic properties of the hydrogels were evaluated. The potential of hydrogels applied in drug delivery system was studied by measuring the release property in vitro, taking aspirin as drug model. The results showed that the hydrogel exhibited a sol-gel transition at about 37 celcius, when the volume ratio of CS (20 mg/mL), PNAM (4.0 mg/mL), and SHC (0.4 M) was 1:0.2:0.5; the hydrogel with good mechanical strength and gelation time of 1-3 min in the physiological conditions was obtained. The hydrogels prepared with high SHC concentration or more gel agents showed shorter gelation time and better thermostability. The hydrogel presented a 1-day sustained release of aspirin with no significant burst release in vitro. The release properties demonstrated that the hydrogels released aspirin in a sustained manner, about 87% in 24 h. L929 cells had good survival and proliferative rates within CS-PNAM/SHC hydrogel after 24 h, showing excellent biocompatibility. Therefore, the injectable thermos-responsive hydrogels formed by CS-PNAM/SHC and loaded with aspirin turned into a smart drug delivery system, showing great potential for controlled release.