Study On The Aggregation Structure Of Anionic Polypeptide Polymers

In this paper,we synthesized random copolymers containing hydrophilic polyethylene glycol monomethyl ether?mPEG?,hydrophobic polyvaline?PV?and ionic polyglutamic acid?PLGlu?.By ¹H NMR,TEM and FTIR characterizations,the secondary structure and self-assembly behavior of a series of copolymers with different hydrophilic and hydrophobic segment lengths were studied.Then,a hydrogel system with dual responses of temperature and pH was constructed,and its temperature/pH response behavior,aggregate structure,the mechanism of gel transformation and the release behavior in vitro were studied by phase transition temperature,DLS,TEM,FTIR,and¹³C-NMR.First,valine NCA and benzyl glutamate NCA were prepared by reacting with triphosgene.In addition,the hydroxyl group of the polyethylene glycol monomethyl ether was successfully modified to an amino group to obtain mPEG-NH₂.Secondly,we synthesized random copolymers(mPEG₁₆-PLGlu₃/PV₃,mPEG₁₆-PLGlu₄/PV₄,mPEG₁₆-PLGlu₅/PV₅)by ring-opening polymerization using mPEG₁₆-NH₂?Mn=750?as the initiator.The FTIR results showed that the secondary structures of the polymers were mainly composed of?–sheet structures at pH 6.2,pH 6.8 and pH 7.4,and it had a tendency to change from?-sheet to random coil with the increase of pH or chain length of polyamino acid.The self-assembly structures of the three polymers at different pH were studied by TEM characterization.The results showed that when the polymer composition was the same,the aggregate structure changed from fibrous or network structure to spherical micelles with the increasing pH.At the same time,the longer the polyamino acid chain,the less regular the aggregates formed.Finally,a temperature/pH dual-response hydrogel based on mPEG₂₂-PLGlu₅/PV₅was prepared,which had the advantages of good water solubility,suitable gel-transition temperature of 37°C,multiple functional groups and strong pH sensitivity.With the increase of pH,the secondary structure of polymer solution has a tendency to change from mainly?-sheet to the coexist of?-helix,?-sheet,random coil,and?-turn.The sol-gel transition process was mainly due to the dehydration of mPEG,while the changeable size and morphology of the copolymer aggregates with pH accounted for the pH sensitivity of the system.Finally,the in vitro drug release behavior of the drug-loaded hydrogel showed that the drug release rate at pH=5.7 was significantly slower than that at pH=7.4.This temperature/pH double-sensitive hydrogel system was expected to be applied in injectable gels and targeted drug delivery.