| Biodegradable thermogelling hydrogel that is a flowing liquid at low temperature, but occurs sol-gel transition when the temperature rises, is a semi-solid drug delivery carrier containing non-covalent crosslinking network. This new hydrogel has important applications in drug delivery fields due to the hydrophilicity and biocompability of the material. In this paper we synthesized poly(ethylene glycol)-poly(amino acid) and and poly(ethylene glycol)-b-poly(lactic acid-r-amino acid) copolymers by solution or melt polymerization, and studied their chemical structures and properties by1H-NMR, FTIR, GPC, dynamic rheometry, sol-gel transition et al.Firstly, PEG with two terminal hydroxyl groups was modified and the terminal groups were converted to amino groups. The conversion yield is almost100%with no obvious chain cleavage or coupling occurred during the modification process.Secondly, amino acid NCAs have been prepared using amino acids by the means of triphosgene. The ease of NCA ring closure is as follow:PheNCA> LeuNCA>ValNCA>AlaNCA. This trend is in agreement with the side chain length of amino acid, which also determined the yield and purity of the NCA products.Thirdly, the two-component amphiphilic poly(ethylene glycol)-poly(amino acid) block copolymers were synthesized by the ring-opening polymerization of amino acid NCAs using PEG containing two amino end groups as the initiator.Finally, the two-component poly(lactic acid-r-amino acid) random copolymers and three-component poly(ethylene glycol)-b-poly(lactic acid-r-amino acid) block copolymers were synthesized by melt copolymerization. By selection of appropriate amino acid unit and change of the chain length, we acquired for the first time the themogelling poly(ethylene glycol)-b-poly(lactic acid-r-leucine)(PEG-P(LA-AA)) copolymer that exhibited well-defined sol-gel transition.20wt%aqueous solution of PEG-P(LA-AA) copolymer showed a sol-gel transition at the temperature of29℃and stable gel at the temperature of37℃, which can be used as injectable hydrogel.In summary, we synthesized new types of biodegradable two-component and three-component copolymers containing amino acid units and acquired new thermogelling copolymer with suitable sol-gel transition. The hydrogel is expected to combine the well degradability of polyester and relatively strong coordination interaction of poly(amino acid) for the development of a valuable new type of injectable materials for drug delivery and tissue engineering applications. |
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