Synthesis, Micellization And Gelation Behavior Of Temperature-sensitive Graft Copolymer [PCL-gP(MEO 2 MA-co-OEGMA)]

Polycaprolactone ?PCL? as a kind of aliphatic polyesters are important biomaterials contributing to its biodegradability, biocompatibility, immunity-less, nontoxicity, and obtained the United States food and drug administration ?FDA? approved. Due to it's so much superior properties, PCL have attracted considerable attention in the fields of biochemistry and biomedicine in drug delivery and tissue engineering. However, crystallinity and hydrophobicity go against the potential application in drug delivery to take advantage of the benefits offered by PCL.2-?2-methoxyethoxy?ethyl methacrylate ?MEO₂MA? and oligo?ethylene glycol? methacrylate) ?OEGMA? could be randomly composed of copolymer P?MEO₂MA-co-OEGMA? with hydrophilic and temperature responsive as PEG analogues. Adujsted the variations of the feed ratio of the MEO₂MA and OEGMA comonomers in copolymerization process, the temperature responsive polymers that present lower critical solution temperature ?LCST? values vary from 26 to 90? can be easily realized. The polymer P?MEO₂MA-co-OEGMA? possess so much attractive properties like temperature sensitive, biocompatible, hydrophilic, nontoxicity and by Food and Drug Administration ?FDA? approved, etc. Thus, this kind of polymer has been widely investigated in potential applications as drug delivery, tissue engineering, materials science and biotechnology.In this work, we aimed to synthesize well-defined novel amphiphilic temperature responsive graft polymers PCL-g-P?MEO₂MA-co-OEGMA?, containing PCL analogues P?aCl?CL-co-?CL? as the hydrophobic backbone, and the hydrophilic side-chain PEG analogues P?ME02MA-co-OEGMA?, which based on hydrophobicity of PCL, and hydrophilic ity and temperature-sensitivity of P?MEO₂MA-co-OEGMA?. In this paper, the graft polymer was synthesized by two methods:atom transfer radical polymerization ?ATRP? technology, a combination of click chemistry and reversible addition-fragmentation chain transfer polymerization?RAFT? technology, respectively. Specific work is as follows:?1? First functional P?aCl?CL-co-?CL? was prepared by the ring opening polymerization ?ROP? of?-capro lac tone ??CL? and a-chloro-?-caprolactone ?aCl?CL? in the presence of ethylene glycol; then, PCL-g-P?MEO₂MA-co-OEGMA??Gs? were synthesized via ATRP of MEO₂ MAand OEGMA, and P?aCl?CL-co-?CL? was used as macroinitiator. A series graft polymer with different grafting density and grafting chains length was synthesized by adjusted the variations of the feed ratio of the MEO₂MA, OEGMA and P?aCl?CL-co-?CL? in copolymerization process. The composition and structure of these copolymers were characterized by 1HNMR, FT-IR and GPC analyses. The self-assembly behaviors of these amphiphilic graft copolymers were investigated by UV transmittance, a fluorescence probe method, dynamic light scattering ?DLS? and transmission electron microscopy ?TEM? analyses. The results showed that Gs exhibited the good solubility in water, and was given the low critical temperature ?LCST? at 35?±1??, which closed to human physiological temperature. The copolymer could self-assemble into core-shell micelles in aqueous solution with diverse sizes when changing the environmental temperature. The results also indicated that Gs could have greater hydrophilicity and temperature-sensitivity when increasing the grafting density and grafting chains length. The vial inversion test and rheological test demonstrated that the graft copolymers could trigger the sol-gel transition which also depended on the temperature. The drug release test showed that graft copolymer could control the release of hydrophilic drug.?2? First, the PCL-N₃ and alkyne end of chain transfer agent alkyne-CTA were prepared, respectively. Then, the PCL-g-CTA was synthesized by click chemistry in the presence of PCL-N₃ and alkynyl-CTA. Finally, a series rGs with grafting chains' different length was prepared via RAFT by adjusting the feed ratio of MEO₂MA, OEGMA and initiator. The composition and structure of these copolymers were characterized by 1H NMR, FT-IR and GPC analyses. The solution properties and self-assembly behaviors were investigated, such as transmittance, lower critical solution temperature ?LCST?, critical micell concentration?CMC?, micelles particle sizes and size distributions, the micelles morphology, and so on. The results showed that the longer grafting chains, the better solubility and temperature-responsive the rGs have.