面向栓塞治疗的单分散高弹性可载药水凝胶微球的微流控制备及其性能研究  

Studies on the Microfluidic Preparation and Properties of Monodisperse,Highly Elastic Drug-loading Hydrogel Microspheres Toward Embolization Therapy

作　　者：施超男 郭明雨 Chao-nan Shi;Ming-yu Guo(State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials,Jiangsu Key Laboratory of Advanced Functional Polymers Design and Application,Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis,College of Chemistry,Chemical Engineering and Materials Science,Soochow University,Suzhou 215123)

机构地区：[1]苏州大学材料与化学化工学部新型功能高分子材料国家地方联合工程实验室、江苏省先进功能高分子材料设计及应用重点实验室、苏州市大分子设计与精密合成重点实验室,苏州215123

出　　处：《高分子学报》2024年第3期328-337,共10页Acta Polymerica Sinica

摘　　要：面向栓塞治疗,利用单乳液毛细管微流控装置制备了粒径均一、尺寸可调节的载药弹性水凝胶微球.以丙烯酰胺(AM)和3-磺酸丙基甲基丙烯酸钾盐(SPMA)为单体,与光引发剂、自制大分子胶束多官能度交联剂(MM2),配制成水溶液作为分散相,以光引发剂、表面活性剂溶于液体石蜡作为连续相,在微流控通道内得到单分散内相液滴,随后通过紫外光照交联聚合,生成具有优异弹性的水凝胶微球.三维通道内的压缩实验表明,微球被压缩约60%而不破碎,且可快速恢复原貌.微球能够快速并大量负载阳离子抗癌药物盐酸阿霉素,20 min即可达到载药平衡,且包封率均超过97%,平衡载药量约648 mg/g(干球)、95mg/g(湿球).此外,还对不同粒径载药微球在不同介质中的药物释放行为进行了研究探讨.研究结果为单分散、高弹性和高载药量水凝胶微球的制备,特别是在栓塞微球方面的潜在应用研究奠定了一定的基础.The aim of this paper is to prepare drug-loaded,highly elastic hydrogel microspheres with monodisperse size distribution and adjustable diameters using a single-emulsion capillary microfluidic device for potential embolization therapy.Aqueous solution of acrylamide(AM)and potassium 3-sulfopropyl methacrylate(SPMA)(monomers),water soluble photo initiator and homemade macromolecular(MM2)micelle(multifunctional crosslinking agent)was used as the dispersed(inner)phase.Oil soluble photo initiator and surfactants were dissolved in liquid paraffin wax,used as the continuous(outer)phase.Monodisperse inner-phase droplets were obtained in the microfluidic channel,which was then crosslinked and polymerized by ultraviolet irradiation to produce hydrogel microspheres with excellent elasticity.The obtained microsphere could be 3D compressed within a round capillary tube more than 60%without breaking and could immediately recover to its original state.The microsphere could quickly load the cationic anticancer drug doxorubicin hydrochloride with high capacity,and the encapsulation efficiency exceeded 97%within 20 min.The equilibrium drug loading capacity was about 648 mg/g(dry spheres)and 95 mg/g(wet spheres).In addition,the drug release behaviors of drug loaded microspheres with different particle sizes in different media were also studied and discussed.These results provide some new experimental and theoretical supports for the preparation of monodisperse,highly elastic and high drug loading hydrogel microspheres,especially for their potential application of embolic microspheres.

关 键 词：微流控 单分散微球 弹性水凝胶微球 栓塞微球 

分 类 号：TQ460.4[化学工程—制药化工] TQ427.26