PCL-PEG-based Block Graft Copolymer, Micellization, Gelation And PMAA "click" Gel

Currently, polycaprolactone (PCL), polyethylene glycol (PEG) and their copolymers received widespread attention, primarily because these polymers are not only biodegradable but also excellent biocompatible, they can be applied to the field of medicine, such as tissue engineering, bone repair, drug delivery, and cell therapy. Block copolymer PCL-PEG or PEG-PCL-PEG self-assembled micelles or gels have been widely applied to the drug release experiments. However, when the PCL block is too large, PEG-PCL-PEG or PCL-PEG-PCL block copolymer are insoluble in water, which is because the poor hydrophilic, semi-crystalline of PCL, and it is difficult to function. Thus, the block copolymer has been greatly restricted in medical applications.To solve the above problems, we introduce the functional groups into the hydrophobic PCL chain, changing the structure of the PCL chain. The hydrophilicity of PEG-PCL-PEG or PCL-PEG-PCL block copolymers are improved to meet the needs of all aspects of the medicine field.PMEO2MA and POEGMA, a homopolymer of PEG analogs, is biocompatible and biodegradable and is a PEG analogs homopolymer. Copolymer P(MEO2MA-co-OEGMA) synthesized by atom transfer radical polymerization (ATRP) of MEO2MA and OEGMA, is a hydrophilic and excellent biocompatible copolymer, and is sensitive to the temperature. Therefore P(MEO2MA-co-OEGMA) as a stimulus responsive material is widely used in the hydrogel, microgel and other aspects of self-assembled micelles.This topic launched following research based on the excellent properties of PEG, PCL, and P(MEO2MA-co-OEGMA):1. First, α-chloro-caprolactone (αClεCL) was synthesized by Baeyer-Villiger oxidation rearran gement, then triblock copolymers V(αCεCL-co-εCL)-b-PEG-b-P(αClεCL-co-εCL) (tB) were prepared by ROP of ε-caprolactone (εCL) and α-chloro-ε-caprolactone (αClεCL) in the presence of PEG. It is found that tB triblock copolymers showed strong hydrophobicity, and there is no significant temperature sensitivity. According to the circumstances of this experiment, further research work has been conducted.2. A novel temperature responsive hydrophilic ABA triblock-graft copolymers [PCL-g-P(MEO2MA-co-OEGMA)]-b-PEG-b-[PCL-g-P(MEO2MA-co-OEGMA)] (tBG) were prepared via ATRP of MEO2MA and OEGMA, and the P(αClεCL-co-eCL)-b-PEG-b-P(αClεCL-co-εCL) was used as a macroinitiator. The study found that introducing hydrophilic P(MEO2MA-co-OEGMA) into hydrophobic PCL chain, not only greatly improved the hydrophilic of the block copolymer, but also endowed the temperature sensitivity. A series of tests were used to study self-assembly micellization and gelation behavior of the block graft copolymer in aqueous solution induced by temperature. The synthesized temperature responsive triblock-graft copolymers formed well-defined core-shell micelles as the temperature was above their LCST (ca.35℃). For a given tBG5 aqueous solution (30 wt %), a weak hydrogel was available at 35℃, and its sol-gel transition temperature gradually decreased with increasing concentration.3. First, azide-end function temperature-sensitive [PCL-g-P(MEO2MA-co-OEGMA)]-b-PEG-b-[PCL-g-P(MEO2MA-co-OEGMA)] were prepared by chlorine end-functional P(MEO2MA-co-OEGMA) graft chains on the block-graft copolymers with sodium azide (NaN3). Second, pH-sensitive PMAA polymer were synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT), and then alkynyl-end function PMAA as a cross-linker was prepared by esterification reaction of PMAA and propargyl alcohol. Third, the temperature/pH-responsive hydrogel was prepared by "click" reaction of the synthesized azide-end function tBG and alkynyl-end function PMAA, and was investigated by a series of measurements. The temperature/pH-responsive hydrogel has high mechanical strength and good heat stability.