This study aimed to develop biodegradable calcium alginate microcarriers with uniform particle size and spherical integrity for sustained-release targeting transarterial chemoembolization. To determine related parameters including the ratio of cross-linking volume (sodium alginate: CaCl₂), concentrations of sodium alginate and CaCl₂ solutions, collection distance, flow rate, stirring speed, syringe needle diameter and hardening time to fabricate the microcarriers, the Taguchi method was applied. Using different conditions, a total of 18 groups were prepared. The average size of microspheres from different groups was estimated as ~ 2 mm (range 1.1 to 1.6 mm). Signal-to-noise ratio analysis showed the optimal spherical integrity (F1) achieved when the above parameters were designed as 0.1, 2.5 wt%, 6 wt%, 8 cm, 30 mL/h, 150 rpm, 0.25 mm and 2 h, respectively. The best (F1), middle (F2) and worst (F3) groups were used for further experiments. Fourier-transform infrared spectroscopy spectrum showed that F1, F2 and F3 conformations were distinct from original sodium alginate. Drug-loaded calcium alginate microcarriers demonstrated rougher surfaces compared to microspheres without drug under transmission electron microscopy. Compared to pH 7.4, swelling rates in PBS were decreased at pH 6.5. Encapsulation and loaded efficiencies of the Dox-loaded microcarriers were estimated as ~ 40.617% and ~ 3.517%. In vitro experiments indicated that the F1 Dox-loaded microcarriers provide a well sustained-release efficacy for about two weeks at 37 °C in PBS. Treatments of calcium alginate microcarriers without the Dox in two distinct hepatocellular carcinoma-derived cell lines, Huh-7 and Hep-3B, indicated that these microcarriers were non-toxic. The Dox-loaded microcarriers displayed sustained-release capacity and reduced cell viabilities to ~ 30% in both cell lines on Day 12.

The objective of this study aimed to develop biodegradable calcium alginate microspheres carrying doxorubicin (Dox) at the micrometer-scale for sustained release and the capacity of pH regulatory for transarterial chemoembolization. Ultrasonic atomization and CaCl₂ cross-linking technologies were used to prepare the microspheres. A 4-by-5 experiment was first designed to identify imperative parameters. The concentration of CaCl₂ and the flow rate of the pump were found to be critical to generate microspheres with a constant volume median diameter (~39 μm) across five groups with different alginate: NaHCO₃ ratios using each corresponding flow rate. In each group, the encapsulation efficiency was positively correlated to the Dox-loading %. Fourier-transform infrared spectroscopy showed that NaHCO₃ and Dox were step-by-step incorporated into the calcium alginate microspheres successfully. Microspheres containing alginate: NaHCO₃ = 1 exhibited rough and porous surfaces, high Young’s modulus, and hardness. In each group with the same alginate: NaHCO₃ ratio, the swelling rates of microspheres were higher in PBS containing 10% FBS compared to those in PBS alone. Microspheres with relatively high NaHCO₃ concentrations in PBS containing 10% FBS maintained better physiological pH and higher accumulated Dox release ratios. In two distinct hepatocellular carcinoma-derived cell lines, treatments with microspheres carrying Dox demonstrated that the cell viabilities decreased in groups with relatively high NaHCO₃ ratios in time- and dose-dependent manners. Our results suggested that biodegradable alginate microspheres containing relatively high NaHCO₃ concentrations improved the cytotoxicity effects in vitro.

Purpose: To evaluate treatment response, survival and safety of a novel TACE using combination of ethanol-Lipiodol mixture and drug-eluting beads in patients with large unresectable HCC, single tumor > 8 cm or multiple tumors with the largest tumor diameter > 5 cm and total tumor diameter > 10 cm. Patients and Methods: Between June 2016 and February 2020, a total of 27 patients were enrolled in this retrospective cohort study. Treatment response was assessed at first month after the treatment; progression-free survival (PFS) and overall survival (OS) were evaluated. The prognostic factors associated with patient survival were statistically analyzed by the Cox regression model. Adverse events were recorded. Results: The maximum diameter of the tumors ranged from 5 cm to 17 cm (mean 10.48 cm). The objective response and disease control rates were 56% and 78%, respectively, at 1-month follow-up. The median survival time was 15.9 months (95% CI, 9.03– 34.76 months). The OS rates were 76.9% at six months, 65.2% at one year and 44.8% at two years. AFP > 400 ng/mL (p = 0.0306), maximum tumor size > 10cm (p = 0.0240) were potential risk factors for OS. Regarding safety, major complications occurred in one patient (1/27, 3.7%), presenting with transient hepatic encephalopathy. Conclusion: Combined DEB-TACE appeared to have favorable objective tumor response. It can be an effective treatment option for large unresectable HCC.

Background: Since the advent of a new generation of inflow-sensitive inversion recovery (IFIR) technology, three-dimensional non-contrast-enhanced magnetic resonance angiography is being used to obtain hepatic vessel images without applying gadolinium contrast agent. The purpose of this study was to explore the diagnostic efficacy of non-contrast-enhanced magnetic resonance angiography (non-CE MRA), contrast-enhanced magnetic resonance angiography (CMRA), and computed tomography angiography (CTA) in the preoperative evaluation of living liver donors. Methods: A total of 43 liver donor candidates who were evaluated for living donor liver transplantation completed examinations. Donors’ age, gender, renal function (eGFR), and previous CTA and imaging were recorded before non-CE MRA and CMRA. CTA images were used as the standard. Results: Five different classifications of hepatic artery patterns (types I, III, V, VI, VIII) and three different classifications of portal vein patterns (types I, II, and III) were identified among 43 candidates. The pretransplant vascular anatomy was well identified using combined non-CE MRA and CMRA of hepatic arteries (100%), PVs (98%), and hepatic veins (100%) compared with CTA images. Non-CE MRA images had significantly stronger contrast signal intensity of portal veins (p < 0.01) and hepatic veins (p < 0.01) than CMRA. No differences were found in signal intensity of the hepatic artery between non-CE MRA and CMRA. Conclusion: Combined non-CE MRA and CMRA demonstrate comparable diagnostic ability to CTA and provide enhanced biliary anatomy information that assures optimum donor safety.