PEG-PCL-based Block - Synthesis And Click On Chemical Crosslinking Graft Copolymer

Polyethyleneglycol (PEG) and polycaprolactone (PCL) have been extensively used to pharmaceutical, biological, and tissue engineering field. As a hydrophilic agent, PEG could link with hydrophobic polymers to obtain amphiphilic copolymers such as PEG-b-PCL-b-PEG triblock copolymers. So far there are many reports about PEG-b-PC L-b-PEG triblock copolymers, which show that the block polymers can assembly to micelles under a certain condition, and the micelles could be suitable for delivering drugs to specific sites such as inflammatory tissues.Up to now, the study on the block-graft copolymers of PEG and PCL is very limited. In order to solve the solubility of the PEG-b-PCL-b-PEG triblock polymer in water, to improve the triblock copolymers hydrophilic, at the same time to endow the PEG-b-PC L-b-PEG triblock copolymers with temperature sensitivity, from a view of molecular design, we suggest to introduce hydrophilic temperature responsive graft chains P(MEO2MA-co-OEGMA) to synthesize a novel triblock-graft copolymers PEG-b-[PCL-g-P(MEO2MA-co-OEGMA)]-b-PEG.The situ injectable hydrogel is a kind of polymer material crosslinked by physical or chemical crosslinking, which can load active cells or drug to the designated position. The environmental sensitive polymer can be used to obtain the sensitivity hydrogel. Using the "Click" Chemistry to prepare situ injectable hydrogel is a very effective method.On the basis of the studies above, polyethyleneglycol (PEG), polycaprolactone (PCL),2-(2-Methoxyethoxy)ethyl methacrylate (MEO2MA), oligo (ethylene glycol) methacrylate (OEGMA) and2-hydroxyethyl methacrylate (HEMA) were used to synthesize triblock-graft copolymer PEG-b-[PCL-g-P(MEO2MA-co-OEGMA)]-b-PEG, random compolymers P(HEMA-co-MEO2MA-co-OEGMA), random compolymers hydrogels, and the properties of their aqueous solutions were studied. The main results of this thesis are as follow:1. The triblock PEG-b-P(αClCL-co-CL)-b-PEG polymers were synthesized by ring-opening polymerization(ROP). The properties of aqueous solution were studied. The results show that the block polymer showed a strong hydrophobicity, and not have temperature sensitivities.2. A series of triblock-graft copolymers PEG-b-[PCL-g-P(MEO2MA-co-OEGMA)]-b-PEG were synthesized by combination of ring-opening polymerization(ROP) and atomic transfer radical polymerization(ATRP). The temperature sensitivities of the triblock-graft copolymer aqueous solutions were investigated by transmittance measurements, viscosity, laser particle size analysis, and transmission electron microscope. The results show that the triblock-graft copolymers have temperature sensitivities, the micellization of triblock copolymers can be realized by changing of temperature. Last, sol-to-gel transition of the triblock-graft copolymers solutions were determined by the test tube inverting method.3. A temperature sensitive hydrogel was prepared by click chemistry between the azide groups on the PEG-b-[PCL-g-P(MEO2MA-co-OEGMA)]-b-PEG copolymer chains and the alkynyl groups on the P(HEMA-co-MEO2MA-co-OEGMA) chains. The microstructures of copolymer hydrogel were characterized by scanning electron microscopy (SEM), swelling properties and temperature sensitivities of hydrogels were studied by weighing method. The drug loading properties and drug delivery of the hydrogel were studied. The results show that the pore size of hydrogel network were small, and the copolymer hydrogels have temperature sensitivities. The hydrogel could be used for the drug release or drug loading.