Preparation of a modified silk-based gel/microsphere composite as a potential hepatic arterial embolization agent

Abstract

Transcatheter arterial chemoembolization (TACE) is an effective method for treating hepatocellular carcinoma (HCC). In this study, chitosan (CS), sodium glycerophosphate (GP), and sodium alginate (SA) were used as the main raw materials to develop clinically non-degradable embolization microspheres (Ms). Chitosan/sodium alginate embolization Ms. were generated using an emulsification cross-linking method. The Ms. were then uniformly dispersed in CS/GP temperature-sensitive gels to produce Gel/Ms. composite embolic agents. The results showed that Gel/Ms. had good morphology and a neatly arranged three-dimensional structure, and the Ms. dispersed in the Gel as evidenced by SEM. Furthermore, Gel/Ms. has good blood compatibility, with a hemolysis rate of ≤5 %. The cytotoxicity experiments have also proven its excellent cell compatibility. The degradation rate of Gel/Ms. was 58.869 ± 1.754 % within 4 weeks, indicating that Gel/Ms. had good degradation performance matching its drug release purpose. The Gel/Ms. adheres better at the target site than Ms. alone and releases the drug steadily over a long period, and the maximum release rate of Gel/Ms. within 8 h was 38.33 ± 1.528 %, and within 168 h was 81.266 ± 1.193 %. Overall, Gel/Ms. demonstrate better slow drug release, reduced sudden drug release, prolonged drug action time at the target site, and reduced toxic side effects on the body compared to Gel alone.