Microfluidic Controllable Preparation of Iodine‐131‐Labeled Microspheres for Radioembolization Therapy of Liver Tumors

Abstract

Transcatheter arterial radioembolization (TARE) is of great significance for the treatment of advanced hepatocellular carcinoma (HCC). However, the existing radioembolic microspheres still have problems such as non‐degradability, non‐uniform size, and inability to directly monitor in vivo, which hinders the development of TARE. In this paper, a novel radioembolic agent, 131I‐labeled methacrylated gelatin microspheres (131I‐GMs), is prepared for the treatment of HCC. Water‐in‐oil (W/O) emulsion templates are prepared by a simple one‐step microfluidic method to obtain methacrylated gelatin microspheres (GMs) after UV irradiation. A series of GMs with uniform and controllable size is obtained by adjusting the flow rate of each fluid. Both air‐dried and freeze‐dried GMs can quickly restore their original shape and size, and still have good monodispersity, elasticity, and biocompatibility. The radiolabeling experiments show that 131I can efficiently bind to GMs by chloramine‐T method, and the obtained 131I‐GMs have good radioactive stability in vitro. The results of in vivo TARE treatment in rats show that 131I‐GMs can be well retained in the hepatic artery and have a good inhibitory effect on the progression of liver cancer, showing the potential for the treatment of HCC.

Polymer Microspheres and Their Application in Cancer Diagnosis and Treatment

“…Common geometries used for microsphere preparation include T-shaped, co-flow, and flow-focused channels. Jiang et al demonstrated the successful preparation of gelatin methacrylate microspheres using a one-step microfluidic technique [ 48 ]. The method allows for precise control of fluid flow rates, resulting in uniform and reproducible microspheres.…”

“…Filipin proteins and sericin proteins rich in tyrosine have been used for chelating 177 Lu and 131 I, respectively [ 30 , 91 ]. GelMA, with tyrosine-rich residues, was successfully grafted onto microspheres, producing 131 I-labeled GelMA radiolabeled microspheres ( 131 I-GMs), enhancing radionuclide stability and reducing leakage [ 48 ].…”

“…As a result, there is a growing focus on the research and development of biodegradable materials. Chitosan microspheres [ 39 ], sodium alginate microspheres [ 18 ], filipin protein microspheres [ 30 , 91 ], and CelMA microspheres [ 48 ] are among the widely utilized options. Apart from biodegradability and good biocompatibility, which are necessary for microsphere re-embolization, uniform and controllable size, as well as good elasticity, are also crucial characteristics for radioactive microspheres [ 48 ].…”

“…Chitosan microspheres [ 39 ], sodium alginate microspheres [ 18 ], filipin protein microspheres [ 30 , 91 ], and CelMA microspheres [ 48 ] are among the widely utilized options. Apart from biodegradability and good biocompatibility, which are necessary for microsphere re-embolization, uniform and controllable size, as well as good elasticity, are also crucial characteristics for radioactive microspheres [ 48 ]. Microspheres with uneven sizes tend to accumulate in proximal vessels, impacting the distal therapeutic outcomes, while insufficient elasticity can hinder smooth injection due to catheter blockage.…”

Microfluidic Fabrication of Monodisperse Hyaluronic Acid Microspheres with Excellent Biocompatibility and Tunable Physicochemical Properties

“…However, the sizes of the HA microspheres prepared by stirring or spray drying methods are not uniform. Microfluidic technology, which can generate monodisperse and controllable droplets by controlling the dimensions of the device and the flow rates of fluids, can be used to fabricate monodisperse HA microspheres. − Shendi et al modified HA with DVS first, reconstructed the lyophilized VS-HA hydrogel precursor in phosphate-buffered solution (PBS) containing 0.1% Irgacure 2959 (I2959) as photo-cross-linker, and then prepared VS-HA droplets by microfluidic technology and fabricated cross-linked hydrogel microspheres through free radical reaction initiated by ultraviolet light. However, this method requires the use of DVS for modifying HA, and DVS has certain toxicities that may cause side effects such as inflammation and edema in the human body. , Yuk et al dissolved HA in sodium hydroxide solution first and stirred for 48 h, then prepared HA droplets by microfluidic technology, and collected the droplets into isobutanol solution containing poly­(ethylene glycol) diglycidyl ether (PEGDE) to obtain HA microspheres through chemical cross-linking.…”