Preparation And Properties Of Multifunctional Poly (Amino Acid) Hydrogels

In recent years, the study of poly(amino acid) materials has attracted a great deal of interests due to a huge potential application prospect of the materials in biomedical fields such as drug delivery system, gene carrier and tissue engineering scaffolds. Because of good biodegradation and biocompatibility, diversity of selected amino acids, and adjustable sequence structure and side chain group, the design of functional and stimuli-responsive materials based on poly(amino acid)s has become a hot research topics..In this thesis, we designed and synthesized a series of thermo-sensitive copolymers containing ionic functional groups or with dual pH and temperature responsiveness, based on the components of poly(ethylene glycol), hydrophobic and ionic poly(amino acid)s. By means of 1H-NMR、DLS、TEM、FTIR、13C-NMR, we studied the assembled structures and sol-gel transition behavior of the copolymers in different pH aqueous solutions and discussed the sol-gel transition mechanism.First of all, the three monomers of amino acid N-carboxyl-α-amino anhydrides(NCAs) have been prepared using amino acids of valine, benzyloxycarbonyl-lysine and glutamic acid by the means of triphosgene. At the same time, the terminal hydroxyl group of α-Methoxy-amino-poly(ethylene glycol)( mPEG-OH) was modified to amino group(mPEG-NH2), which would be used as an initiator to polymerized NCAs.Then the cationic poly(ethylene glycol)-poly(L-lysine)-poly(L-valine) tri-block copolymer(mPEG22-PLL2-PV7) was synthesized by sequence ring-opening polymerization of benzyloxycarbonyl-lysine NCA and valine NCA in the presence of mPEG-NH2,followed by deprotection using trifluoroacetic acid and hydrogen bromide acetic acid solution. NMR spectrum showed that the copolymer composition was in agreement with the expected value, and the lysine side protection group was removed completely. The copolymer displayed a predominant β-sheet secondary structure, and could self-assemble into spherical structure in aqueous solutions, with the size of aggregates increasing with the increase of pH value. The sol-gel transition behavior of the copolymer aqueous solution has shown both pH and temperature responsiveness. The pH responsive behavior was related to the ionization degree of lysine and the temperature responsiveness was due to the dehydration effect of poly(ethylene glycol) segment.Finally, the anionic poly(ethylene glycol)-poly(L-glutamic acid)-poly(L-valine) tri-block copolymer(mPEG22-PGA3-PV7)was synthesized by the above similar method, using L-glutamate NCA instead of benzyloxycarbonyl-lysine NCA. In the neutral condition, the copolymer could form a good sol solution, which exhibited good sol-gel transition at higher temperature. However, under the acidic condition(pH less than 6), the copolymer had a significant aggregation, and the sol-gel transition behavior of the copolymer aqueous solution did not shown obvious pH response characteristics.