Impact of particle size of multivesicular liposomes on the embolic and therapeutic effects in rabbit VX2 liver tumor.

Abstract

Transcatheter arterial chemoembolization (TACE) is usually considered more efficacious in the local treatment of parenchyma-sparing hepatocellular carcinoma (HCC). At present, embolic agents commonly used in TACE, include DC pellets, Hepasphere, Lipiodol, etc. Except that iodine oil is a viscous fluid embolic agent, other solid microsphere particles used clinically range from 70 to 700 µm, among which 100 to 300 µm is the most commonly used. With the technology development of micro-invasive interventional therapy, the specific distal embolization through TACE to occlude tumor arterial blood supply in patients with HCC is also required more accurately. Effective terminal embolization is considered to be a preferred option for TACE therapy due to significantly improving the survival rate of patients and preserving liver function. In this article, we prepared the multifunctional multivesicular liposomes (IVO-DOX-MVLs) (<100 µm) that can simultaneously encapsulate ioversol and doxorubicin based on the high-phase transition temperature (T_m) lipid ingredients, and evaluated its local artery embolization and therapeutic effect in rabbit VX-2 tumor model. The influence of particle size on occlusion and therapeutic effect of MVLs on rabbit VX-2 liver tumor models were well evaluated, including the tumor volume change, tumor growth rate, and necrosis rate, which were evaluated by magnetic resonance (MR). MVL samples with average particle size distribution of 50-60 µm exhibited fewer off-target embolization. Through TACE, IVO-DOX-MVLs were directly transported to the tumor tissues, playing roles of embolization performance, CT imaging effect, and local tumor killing effect. The feasibility of MVLs as a multifunctional embolic agent in its clinical application can be further improved by optimization of lipid composition and preparation process.