Sorafenib and 2,3,5-triiodobenzoic acid-loaded imageable microspheres for transarterial embolization of a liver tumor

Abstract

Sorafenib (SOF; an angiogenesis inhibitor) and 2,3,5-triiodobenzoic acid (TIBA; a contrast agent for computed tomography imaging)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were fabricated. Embolization, drug delivery, and tracing the distribution of MSs for liver cancer therapy were accomplished with the developed MSs after their intra-arterial (IA) administration. SOF/TIBA/PLGA MSs with 24.8–28.5 µm mean diameters were prepared, and the sustained release of SOF from MSs was observed. Lower systemic exposure (represented as the area under the curve [AUC]) and maximum drug concentration in plasma (Cmax) values of the SOF/TIBA/PLGA MSs group (IA administration, 1 mg/kg) in the results of the pharmacokinetic study imply alleviated unwanted systemic effects (e.g., hand and foot syndrome), compared to the SOF solution group (oral administration, 10 mg/kg). In a rat hepatoma model, the increase of microvessel density (MVD) following arterial embolization (i.e., reactive angiogenesis) was partially limited by SOF/TIBA/PLGA MSs. This resulted in the SOF/TIBA/PLGA MSs group (IA administration, single dosing, 1 mg/kg) showing a smaller tumor size increase and viable tumor portion compared to the TIBA/PLGA MSs group. These findings suggest that a developed SOF/TIBA/PLGA MS can be a promising therapeutic system for liver cancer using a transarterial embolization strategy.

Application of PLGA-ion exchange resin microcapsules of sulfasalazine ‎for embolization therapy

“…The results showed the gradual biodegradation of PLGA coat of selected formula in human serum where pores formed upon incubation and became more clear with time causing gradual controlled drug release with time accordingly. Similar results obtained with Sorafenib loaded imageable microspheres for embolization where PLGA polymer degradation gave lactic acid and glycolic acid in the biological fluid 39,40 as shown in Fig. 9.…”

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

“…In this study, the HACE/DOX composite-embedded MS was fabricated using a modified emulsification method. In our previous studies (Choi et al., 2015 , 2017 ), PLGA-based MSs were developed for the locoregional delivery of anticancer agents to a liver tumor via the IA route. For the efficient entrapment of anticancer drugs (i.e.…”

“…Notably, in our recent study (Choi et al., 2017 ), TIBA was added to MSs as a CT imaging contrast agent to monitor the in vivo fate of MSs after their IA administration. Although the sustained release property of the drug from PLGA-based MSs has already been presented in previous studies (Choi et al., 2015 , 2017 ), their selective uptake into liver cancer cells has not been investigated. The DOX/HACE composite and TIBA were incorporated into the PLGA MS in this study and the release of the DOX/HACE-based nanoassembly from MSs was expected.…”

“…The IA administration of the MS formulation was performed by an experienced interventional radiologist according to published protocols (Choi et al., 2015 , 2017 ). Under anesthesia via the intramuscular injection of zolazepam (5 mg/kg, Zoletil ® ; Virbac, Carros, France) and xylazine (10 mg/kg, Rompun ® ; Bayer-Schering Pharma, Berlin, Germany), a 1.6-French microcatheter (Nano 1.6; Create Medic, Yokohama, Japan) was inserted into the carotid artery.…”

“…Alteration in the volume of liver tumor in control, DOX MS, and DOX/HACE MS groups was detected by clinical MR scanner on day 0, 3, and 7. MR image was obtained with a T2-weighted imaging sequence (bandwidth = 199 Hz/pixel; field of view = 80 × 65 mm; matrix = 256 × 177; repetition time/echo time = 4180/77 msec; slice thickness = 2 mm) (Choi et al., 2017 ). Tumor volume ( V , mm 3 ) was calculated with longer diameter ( a , mm) and shorter diameter ( b , mm) by the following formula: …”