Synthesis Of Insulin Delivery System Containing Polypeptides Fragments And Study Of Secondary On Glucose-responsive Behavior

In order to solve the problem that the salt tolerance of the glucose-responsive insulin delivery system is limited and the stability is poor under the physiological condition(pH 7.4,0.15 M PBS),this paper adopts the method of co-assembly to form the composite nanoparticles to the original sugar The polypeptides have very good biocompatibility and biodegradability.At the same time,the specific sequence of synthetic peptides synthesized by artificial design can form a unique secondary conformation by self-assembly.The presence of secondary conformation can confer the characteristics and advantages that individual nanoparticles do not have,which is of potential value in solving the instability of the glucose-response system.In this article,we will focus on the unique structure of the complex nanoparticles formed by co-assembly of two types of amphiphilic copolymers,one of which is polypeptideto,and then further elucidate the effect of different secondary structures on the properties of the complex nanoparticles.The details are as follows:1?The complex nanoparticles formed by 75%mass fraction of mPEG-b-PBLG20 with mPEG-b-PPBDEMA75 were stable without disintegration under physiological conditions(0.15 M PBS,pH 7.4).This phenomenon was analyzed from circular dichroism spectroscopy,FTIR and DLS.It was found that the complex nanoparticles had secondary structure due to the introduction of polypeptides.With 75%of the optimal ratio,the proportion of a-helix and ?-sheet is more than 50%,which is the dominant conformation of complex nanoparticles.And the hydrogen bonding force as maintenance of these two secondary conformation makes the salt tolerance of the complex nanoparticles up to 0.15 M.At the same time,PEG-b-PLA and PEG-b-PS were designed as the comparative materials without the secondary conformation but strong hydrophobic driving force.It was found that the complex nanoparticles formed by co-assembly with mPEG-b-PPBDEMA75 were extremely unstable and the glucose-response behavior was uncontrollable at physiological salt concentration.On the other hand,maintaining the glucose-response polymer unchanged,we synthesized different repeating units of the peptides.As the same 75%mass percentage of mPEG-b-PBLG with mPEG-b-PPBDEMA75,the complex nanoparticles formed by co-assembly can still be stable under the physiological conditions and won't be collapsed because of high salt ion strength,while the sensitivity to identify different sugar concentrations still exists.That is,at the normal blood glucose concentration the drug molecules does not release,but at high blood sugar concentration drug molecules perform the stable release,which achieve intelligent controllable release behavior,and achieve the purpose of treatment of disease.2?we synthesized two random block copolymers mPEG-b-(PBLG20-co-PLG40)60(RCP-1)and mPEG-b-(PBLG48-co-PLG 12)60(RCP-2)from deprotection of the polymer framework mPEG-b-PBLG60.The structure of the compolymers was characterized by NMR,and the critical micelle concentration was measured by ultraviolet turbidity method.Finally,the complex nanoparticles were co-assembled to obtain particle size uniform stability according to the 75%mass percentage of RCP-1 and RCP-2 with mPEG-b-PPBDEMA75,respectively.Compared with a-helix dominance in nanoparticles formed by self-assembly of mPEG-b-PBLG60,RCP-1 and RCP-2 show a predominant phenomenon of random coil and ?-sheet at pH 7.4.It was found that the salt tolerance of RCP-1 complex nanoparticles was reduced to 0.05 M,and RCP-2 complex nanoparticles could be only 0.10 M phosphate buffer solution.This indicates that the composite nanoparticles exhibit different conformations due to the different polymer structures and the difference of the interaction between the different conformations results in different salt tolerance of the nanoparticles.