Injectable PNIPAAm-Based Liquid Embolic Materials

In this work, two types of injectable thermosensitive hydrogels, poly(N-isopropylacrylamide-co-vinyl laurate) (P(NIPAAm-co-VL)) and poly (N-isopropylacrylamide-co-N-propylacrylamide-co-vinyl pyrrolidone) (PNINAVP), were preparedby free radical copolymerization. The main contents include four parts as follows:(1) The formation of P(NIPAAm-co-VL) was confirmed by FTIR and 1H NMR.The number average molecular weight of this copolymer determined by GPC wasabout a few thousand. The clouding point (CP) and low critical solution temperature(LCST) were determined by turbidimetry and differential scanning calorimetry (DSC),respectively. All the results indicated that the macroscopic sol-gel transitiontemperature decreased upon increasing solution concentrations and VL contents in thecopolymer. The CP and LCST of copolymer solution were also lowered along withthe increment of VL contents.(2) PNINAVP hydrogel showed a prominent thermoresponsive behavior, and thetransition times of sol to gel and gel to sol were within 1 min. The shear moduli andviscosity were examined by a rheometer. With the increase of N-propylacrylamidecontents in the copolymer, the CP and LCST decreased. Meanwhile, the transitionfrom sol to gel was faster, while the gel-sol time became longer near bodytemperature. After the sol-gel transition, the shear moduli and viscosity of thecopolymer with higher N-propylacrylamide contents were enhanced over onethousand times and nearly one hundred times, respectively. Upon increasing theconcentrations of PNINAVP solution, the shear viscosity was raised markedly, but noevident variation in the CP and LCST was observed. According to requirements ofanimal experiments, a certain amount of iohexol was added to the copolymer solution.During the sol-gel transition, the copolymer and iohexol formed an integrated bulkyhydrogel because of the hydrogen bonding between them. The CP and LCST of thissolution increased by 2~3℃, and the shear viscosity rose slightly as well.(3) The simulation experiments for evaluating the transport of embolic agentsand embolization effect were performed. The results revealed that P(NIPAAm-co-VL)could not form the bulky hydrogel due to the excessive hydrophobicity of VLsegments, hinting it was unsuitable for embolization. Whereas, 5% 16:16:1 PNINAVPsol could form the bulky hydrogel after readily passing through the catheter. The gelformed completely occluded the space between glass beads without mass loss,entirely stopping the saline solution flow.(4) 5% 16:16:1 PNINAVP solution was applied to the embolization of the swineretemirabile. The angiograms of the retemirabile were performed immediately, onemonth and two months later after operation. It was shown that this liquid embolicagent was capable of effectively occluding the retemirabile. It seemed that little partof the retemirabile became thicker and could be seen on the angiograms due to theblood from the anastomotica and the occlusion of ascending pharynx artery.