| In order to reduce side effects of drug in the body or to improve the effectiveness of drug against diseases, the targeted drug has become a hot research topic. If the drug carrier is applied to the human body, and the drug released only in the diseased tissue site, not only can effective use of drugs for optimal therapeutic effect, but also no toxic side effects would be produced in other normal parts. The most commonly used environment-sensitive hydrogels (carries) is the type of N-isopropylacrylamide (NIPAM) polymers. However, the swelling/deswelling response rate of PNIPAM hydrogels to the external stimulation is very slow. Sometimes, it even takes a few hours or even several days to achieve the final balance; In addition, general hydrogels have poor mechanical properties: they are more brittle and fragile, difficult to stretch. These factors largely limit their application. Therefore, we need to explore a new preparation method of temperature-sensitive materials, to compensate for the types of temperature-sensitive materials, to explore new composite structure of the gel, to change its temperature sensitive properties of the speed, and to establish new delivery systems. In order to increase the reaction kinetics of hydrogel, several strategies are explored.1. The sandwich-typed hydrogel column is fabricated by three-step process using ice-melting synthesis. This novel hydrogel column which is featured with both ends of linear poly(N-isopropylacrylamide) chains being grafted onto cross-linked PNIPAM chain. To discuss the influence of the reaction pathway triggered to temperature sensing properties of hydrogels, this article will put N,N'-Methylenebisacry- lamide(BIS), ammonium persulfate (APS) into different layers, forming sandwich-typed hydrogel of Type A and Type B. In order to compare the sandwich hydrogel with the ordinary hydrogel , the experiment synthesizes homogeneous Type N. The swelling hydrogel swelling/deswelling kinetics and drug release characteristics of the hydrogel column are studied. The results are shown as followed:①Hydrogels have better temperature sensitive, the phase transited at 33℃;②Swelling-deswelling kinetics of the hydrogels are tested for several times. The results show that mechanical properties of hydrogels are still high and the integrity is kept;③Swelling/deswelling kinetics experiments show that Type B's swelling/ deswelling rate is the highest while Type N is the lowest;④Drug release (NaCl solution) test show that the process of temperature rises from low to high, the salt concentration of outside environment of the three types hydrogels increases correspondingly, Type B grow the most quickly, then Type A, Type N is the slowest, proving that this method can improve the reaction rate of general hydrogel;2. Through reversible addition–fragmentation chain transfer polymerization (RAFT) method, thermo-responsive dendrimer is synthesized. Each step of the reaction is charactered by FI-IR and 1HNMR spectra. And the final synthesis of dendrimers are tested by temperature sensitivity. Experiments show that:①FI-IR and 1HNMR spectra show that the success of every step of the reaction;②They have good temperature sensitivity. The content of styrene and NIPAM influence the phase transition temperature;③They change into a milky white in a short time, and they restored the colorless rapidly, indicating that NIPAM grafted onto the dendrimer can increase the swelling / deswelling rate;3. Through atom transfer radical polymerization (ATRP) method, poly (N-isopropyl acrylamide) is grafted into the gas phase spherical silica (nano-) surface, the chain length and density of the NIPAM can be controlled. Each step of the reaction is characterized by FI-IR, the status of each step of the reaction is shown by scanning electron microscope (SEM) graph, and the temperature sensitivity is finally tested. Preliminary results show success of every step reaction. The influence of reaction conditions to temperature sensitivity still need to be further explored. |
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