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

Song Yi Lee,Jin Woo Choi,Jae-Young Lee,Dae-Duk Kim,Hyo-Cheol Kim,Hyun-Jong Cho

doi:10.1080/10717544.2018.1480673

Song Yi Lee, Jin Woo Choi + Show 4 more

Open Access

https://doi.org/10.1080/10717544.2018.1480673

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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.

Highlights

The complete remission of hepatocellular carcinoma (HCC) is known to be difficult due to disease heterogeneity and its tendencies toward metastasis and recurrence (Dutta & Mahato, 2017)
To the best of our knowledge, this is the first report of a drug-loaded HA nanoassembly-releasing poly(lactic-co-glycolic acid) (PLGA) MS formulation; we systemically evaluated its therapeutic potentials for HCC
The DOX/hyaluronic acid-ceramide (HACE) composite and Triiodobenzoic acid (TIBA) were incorporated into the PLGA MS in this study and the release of the DOX/HACE-based nanoassembly from MSs was expected

Summary

Introduction

The complete remission of hepatocellular carcinoma (HCC) is known to be difficult due to disease heterogeneity and its tendencies toward metastasis and recurrence (Dutta & Mahato, 2017). Various therapeutic approaches (e.g. liver transplantation, surgical resection, local ablation, transarterial chemoembolization (TACE), radiotherapy, and molecular-targeted agents) have been used for the therapy of HCC (Genco et al, 2013; Grandhi et al, 2016; Dutta & Mahato, 2017; Kim, 2017; Lee & Khan, 2017). The application of surgical resection and local ablation has been restricted for patients with large/ multiple tumors, extrahepatic spread of HCC, and decreased hepatic function. In this context, TACE is widely applied to those patients with a minimal invasiveness. Considering the angiogenesis induced by hypoxia following TACE, more elaborate therapeutic approaches are necessary for elevating the anticancer efficacies of TACE and minimizing its toxicities

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