Simulation of in vitro embolization effect of drug-loaded microspheres

Drug-loaded microspheres are widely used in transcatheter arterial chemoembolization (TACE). Controlled drug release from drug-loaded microspheres reduces systemic toxicity, thus necessitating the development of microspheres with controlled release properties. In this study, three different sizes of sodium hyaluronate microspheres (SH) were prepared by a one-step solution drying method using 1,4-butanediol diglycidyl ether (BDDE) as a crosslinking agent. The average sizes of the three SH microspheres (small, medium and large) were 410 μm, 550 μm and 750 μm, respectively. The morphology of the small-sized SH microspheres (SS-SH) was solid spherical; the medium-sized SH microspheres (MS-SH) were semi-hollow spherical; and the large-sized SH microspheres (LS-SH) had a bowl with an opening on one side and a cavity inside. A drug-loaded microsphere (DOX@SH) was prepared by immersing SH microspheres in a doxorubicin hydrochloride (DOX) solution. The average size of the three DOX@SH microspheres increased to 607 μm, 876 μm and 1187 μm, respectively. The encapsulation efficiencies of small, medium and large-sized SH microspheres reached 97.09 %, 96.73 % and 74.87 % at 2 h in a 2 mg/mL DOX solution. The maximum drug loadings of the small, medium and large-sized SH microspheres were 0.38, 0.38 and 0.33 mg DOX/mg SH, respectively. All sizes of DOX@SH microspheres could be controlled and sustained to release and reach equilibrium after 48 h. The cumulative release rates of small, medium and large-sized DOX@SH microspheres (SS-DOX@SH, MS-DOX@SH and LS-DOX@SH) at 72 h were 24.3 %, 28.1 % and 33.8 % in a release medium of pH 6.5, respectively. Blood compatibility and cytotoxicity tests demonstrated that SH microspheres exhibit good biocompatibility. The cytotoxicity of DOX@SH microspheres to HepG2 cells and the uptake of DOX in HepG2 cells showed effective anti-tumor activity. Simulated embolization in vitro experiments indicated that the small-sized DOX@SH microspheres had a good embolization effect for 500–800 μm and 300–500 μm blood vessels. These findings indicate that the newly developed DOX@SH microspheres can be used as a promising drug-loaded embolization agent to enhance the treatment of hepatocellular carcinoma.