Behavioral Study Of Glucose-responsive Insulin Delivery System Including Polypeptides Structure

This article was mainly based on the polypeptides secondary structure.Due to different secondary structure of assembled nanoparticles,its has different response behaviors.It focused on polypeptides secondary structure for the stability and glucose-responsive behavior of the nanoparticles.Meanwhile,synthesizing two kinds of polypeptides with glucose-responsive fragments,its has not only excellent biocompatibility and degradability,but also can use to glucose-responsive insulin delivery.We used this two materials layer-by-layer assembly or co-assembly,then studied their behaviors.Detail as follows:1.We obtained two amphiphilic copolymers,mPEG110-b-PPBDEMA,mPEG110-b-PBLG,mPEG110-b-(PBLG-co-PGA),then co-assembly formed glucose-responsive complex nanoparticles,this work describes the different effect of the different secondary structural architecture of the polypeptides blocks on the stability and glucose-responsive of the complex nanoparticles.we used the circular dichroism and insulin release under different stimuli to carry out the nanoparticles behavior.We found that the stability and glucose sensitivity of complex nanoparticles are closely related with the polypeptides blocks secondary structure.The complex nanoparticles which has dominant a-helix structure exhibit better potential to glycemic control and to reduce the incidence of hyperglycemic and hypoglycemic via in vitro and in vivo evaluation.2.The glucose-responsive fragments was grafted onto the polypeptides to obtain polypeptides containing glucose-responsive fragments,CP-1(mPEG110-b-(PLL20-EPDM5)),CP-2(mPEG110-b-(PLL14-EPDM1),CP-3(mPEG110-Zb-(PLG20-EPDMA5))and CP-4(mPEG110-b-(PLG18-EPDMA7)).3.Since the two polypeptides has opposite charge,so we used insulin aggregates as charge core(Cinsulin = 0.5 mg/mL,CNaCl = 1.0 M Zeta = 4.9 mV),using positive charge polypeptide(mPEG110-b-(PLG-EPDMA))electrostatic adsorption on the insulin core,the polymer concentration equals lmg/ml and the efficiency is 39.6%.Then,using negative charge polypeptides(mPEG110-b-(PLL-EPDM))electrostatic adsorption on the nanoparticles surface,the polymer concentration equals 1.0 mg/mL and the efficiency is 84.3%.Further research is developing.4.The two polypeptides which containing glucose-responsive fragment were co-assembled,we obtained negative charge nanopaticles under physiological pH by changing the ratio of two polypeptides and surrounding pH.When CP-1:CP-3 = 8:1,the nanoparticle charge is 1.71 mV,charge changed to-7.59 mV under physiological pH.The charge of naoparticles formed by CP-2:CP-4 =10:1 was-3.38 mV.Then we explored the loading insulin complex nanoparticles behavior.