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

Abstract

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 π–π 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.