High-Performance Poly(lactic-co-glycolic acid)-Magnetic Microspheres Prepared by Rotating Membrane Emulsification for Transcatheter Arterial Embolization and Magnetic Ablation in VX₂ Liver Tumors

Abstract

Interventional embolization is a popular minimally invasive vascular therapeutic technique and has been widely applied for hepatocellular carcinoma (HCC) therapy. However, harmful effects caused by transcatheter arterial chemoembolization (TACE) and radioembolization, such as the toxicity of chemotherapy or excessive radiation damage, are serious disadvantages and significantly reduce the therapeutic efficacy. Here, a synergistic therapeutic strategy combined transcatheter arterial embolization and magnetic ablation (TAEMA) by using poly(lactic-co-glycolic acid) (PLGA)-magnetic microspheres (MMs) has been successfully applied to orthotopic VX liver tumors of rabbits. These MMs fabricated by novel rotating membrane emulsification system with well-controlled sizes (100-1000 μm) exhibited extremely low hemolysis ratio and excellent biocompatibility with HepG2 cells and L02 cells. Moreover, experimental results demonstrated that, while exposed to alternating magnetic field (AMF) after TAE, the tumor edge could be heated up by more than 15 °C both in vivo and in vitro, whereas only a negligible increase of temperature was observed in the normal hepatic parenchyma (NHP) nearby. Sufficient temperature increase induces apoptosis of tumor cells. This can further inhibit the tumor angiogenesis and results in necrosis compared to the rabbits only treated with TAE. In stark contrast, tumors rapidly grow and subtotal metastasis occurs in the lungs or kidneys, causing severe complications for rabbits only irradiated under AMF. Importantly, the results from the biochemical examination and the gene expression of relative HCC markers further confirmed that the treatment protocol using PLGA-MMs could achieve good biosafety and excellent therapeutic efficacy, which are promising for liver cancer therapy.

Preparation of microspheres encapsulating sorafenib and catalase and their application in rabbit VX2 liver tumor

“…The experimental use of PLGA MSs for hepatic artery embolization has been reported [18]. PLGA is a copolymer that can be hydrolyzed into biocompatible substances, including lactic acid and glycolic acid monomers [30].…”

“…Some studies have shown that PLGA MSs releases drugs slowly into surrounding tissues through a diffusion mechanism to promote the complete release of the drug, thereby improving the treatment effect of drugs [32]. TACE combined with magnetic PLGA MSs significantly enhanced the delivery of cytotoxic drugs to rabbit liver tumors while reducing the systemic toxicity in the animals [18].…”

“…Recently, microspheres (MSs) composed of the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) have been developed for TACE in the treatment of liver tumors [17]. PLGA has excellent biocompatibility and biodegradability, and has been widely applied in bone tissue engineering [18]. As a drug carrier, PLGA has been approved by the FDA for some clinical treatments [19].…”

Meeting the unmet: from traditional to cutting-edge techniques for poly lactide and poly lactide-co-glycolide microparticle manufacturing

“…The possibility to finely tune size and composition of PLA and PLGA MP by adopting proper multiple emulsification processes affords fabrication of complex composite particles. In this regard, a rotating membrane emulsification system was employed for the preparation of iron nanoparticle loaded PLGA MP for tumor arterial embolization and magnetic ablation (Liang et al 2017).…”

Recovery of metals and complexant in wastewater by shear induced dissociation coupling with ultrafiltration

“…Yi‐Jun Liang et al . prepared PLGA‐magnetic microspheres by rotating membrane . Shear induced dissociation coupling with ultrafiltration (SID‐UF), is a novel method to selectively recover metals and complexant according to the difference of shear stabilities of polymer‐metal complexes .…”