Hyaluronic acid/doxorubicin nanoassembly-releasing microspheres for the transarterial chemoembolization of a liver tumor

Abstract

Doxorubicin (DOX)-loaded, hyaluronic acid-ceramide (HACE) nanoassembly-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were developed for transarterial chemoembolization (TACE) therapy of liver cancer. DOX/HACE MSs with a mean diameter of 27 μm and a spherical shape were prepared based on the modified emulsification method. Their in vitro biodegradability in artificial biological fluids was observed. A more sustained drug release pattern was observed from DOX/HACE MS than from DOX MS at pH 7.4. The cellular internalization efficiency of DOX of the DOX/HACE MS group was higher than that of the DOX MS group in liver cancer cells (HepG2 and McA-RH7777 cells), mainly due to CD44 receptor-mediated endocytosis of the released DOX/HACE nanoassembly. In both HepG2 and McA-RH7777 cells, the antiproliferation and apoptotic potentials of the DOX/HACE MS were significantly higher than those of the DOX MS (p < .05). Notably, in the McA-RH7777 tumor-implanted rat models, a better tumor growth suppression, a lower tumor viable portion, and a higher incidence of apoptosis were presented in the DOX/HACE MS group than in the DOX MS group after intra-arterial (IA) administration. DOX/HACE-based nanoassembly release from the DOX/HACE MS seems to elevate the cellular accumulation of DOX and its anticancer activities. The developed DOX/HACE MS can be used as a drug-loaded HA nanoassembly-releasing MS system for TACE therapy of liver cancer.