Thermosensitive hydrogel drug delivery system containing doxorubicin loaded CS - GO nanocarriers for controlled release drug in situ

Local delivery of antitumour drugs provided a high local concentration, the intention of increased antitumour and decreased systemic therapy. An injectable thermosensitive hydrogel is commonly used as a local drug delivery system (DDS). In this paper, a novel local hydrophilic doxorubicin (DOX) DDS, chitosan functionalised graphene oxide (CS-GO) nanocarriers in polylactide (PLA)-poly( ethylene glycol) (PEG)-PLA thermosensitive hydrogel, was demonstrated. The DOX loaded CS-GO nanocarriers (DOX/CS-GO) were prepared via pi-pi stacking and hydrophobic interactions, which presented a superior loading capacity for DOX, and then DOX/CS-GO were incorporated into the thermosensitive hydrous matrix. The obtained injectable hydrophilic DOX delivery system was flowing sol at ambient temperature but became non-flowing gel at body temperature and can act as a depot for sustained release of DOX in situ. The in vitro cytotoxicity test showed that the PLA-PEG-PLA hydrogel and CS-GO nanocarriers were non-cytotoxic. The obtained CS-GO/DOX nanocarriers not only showed increased cellular uptake but also enhanced cytotoxicity. The in vitro release of PLA-PEG-PLA/(CS-GO/DOX) complexes was sustained for >200 h. These results suggested that this injectable composite hydrogel is a potential candidate as drug carrier and in clinical applications in situ.