Fast thermoresponsive BAB-type HEMA/NIPAAm triblock copolymer solutions for embolization of abnormal blood vessels

Thermoresponsive BAB-type HEMA/NIPAAm triblock copolymers (A = NIPAAm, B = HEMA) were prepared by atomic transfer radical polymerization (ATRP). BAB1-6 with shorter PNIPAAm blocks failed to form stable gel; while a relatively stable gel could be achieved by BAB1-8 with longer PNIPAAm blocks when copolymer aqueous solution was heated up. Introducing radiopaque agent (RA) was shown to slightly increase the transition temperature and gelation time, but the gelling ability was strengthened due to slightly weakening dehydration of copolymer in the mixture of water and RA. BAB1-8 aqueous solution about 5 wt% in the presence of RA was demonstrated to successfully occlude the cerebral rete mirabiles (RMs) and renal arteries of pigs. Within 3-month surgery, no recanalization was observed and the embolized kidney shrank considerably. Histological assay of embolized kidney demonstrated interstitial fibrosis and calcification as well as the thickening of renal small artery. This temperature sensitive copolymer with well-defined architecture holds a great potential as an embolic agent for treating arteriovenous malformations (AVMs) and renal disease due to the design flexibility of ATRP.