Synthesis And Applications Of Modified Interpenetrating Temperature-pH Sensitive Hydrogel

In order to overcome the problems of slow response rate,poor mechanical properties,and single-response problems of traditional intelligent hydrogels,it is an efficient and convenient method to interpenetrate different types of hydrogels.The hydrogel after interpenetration can have several The advantages of these components,to achieve the complementary combination of functional components,is a modification measure with great potential.In this study,a pH-sensitive polyaspartic acid(PASP)hydrogel was interpenetrated into a modified poly(N-isopropylacrylamide-butyl methacrylate)(PNIPAM-BMA)hydrogel matrix that can respond to temperature stimulate,where PNIPAM hydrogels provided the temperature sensitivity to the interpenetrating hydrogel and the modification of the BMA increases the mechanical properties of the interpenetrating hydrogel.The incorporation of the PASP hydrogel not only modified the structure and pore size of the interpenetrated hydrogel network,but also added the pH sensitivity to the interpenetrated hydrogel.Based on this,a novel type of interpenetrating polymer network(PASP/P(NIPAM-BMA))hydrogel was prepared that has both stimuli responsiveness to temperature and pH.Firstly,the prepared interpenetrating(PASP/P(NIPAM-BMA))hydrogels were fully characterized including FT-IR,XRD,SEM,mechanical properties and swelling properties.Secondly,on the basis of characterization,the anticancer drug cytarabine(CYT)as a model drug was encapsulated into(PASP/P(NIPAM-BMA))hydrogel.The in vitro release results showed that the release rate of CYT has a large relationship with the ambient temperature and the pH of the release medium.The difference of the drug release can reach 30%under different conditions,indicated that the prepared interpenetrating hydrogel has a great pH-temperature sensitivity.In the MTT assay,the viability of the 7701 cells and A549 cells after the blank interpenetrating hydrogel extracts were treated for 48 h was above 94%,indicating that all the blank interpenetrating hydrogels were not cytotoxic and had good bioactivity.compatibility.The survival rate of A549 cells treated with the drug-containing hydrogel extract was significantly correlated with the concentration of the drug contained in the hydrogels.The cell viability was reduced,when the drug concentration was increased.At a drug concentration of 5 μg/mL,free drug solutions and the drug solutions released from the hydrogel can kill 63%and 70%of A549 cells,respectively.Whereas,they can kill 85%and 80%of A549 cells when the drug concentration is 40 μg/mL.This result demonstrates that the molecule drug CYT released from the hydrogel still has good biological activity.Finally,in order to further expand the application of the interpenetrating hydrogel,the interpenetrating(PASP/P(NIPAM-BMA))hydrogel was also used in a time temperature indicator(TTI)to optimize the time temperature.Based on the indicator system,the(PASP/P(NIPAM-BMA))hydrogel was used as a dual enzyme immobilization carrier in the time temperature indicator system.The results demonstrate that the use of hydrogel as a carrier of the enzyme over time produces a significant phase change in color without affecting the activity of the enzyme,consistent with the conditions of the time temperature indicator.In conclusion,on the one hand,the prepared interpenetrating(PASP/P(NIPAM-BMA))hydrogel can be used for drug storage and delivery.On the other hand,it can also be used as an effective enzyme carrier for time temperature indicators.Based on these findings,(PASP/P(NIPAM-BMA))hydrogel would be a promising candidate in molecular storage and delivery systems.