Synthesis Of Novel Protein Carrier Based On Phenylboronic Acid And Its Application In The Treatment Of Diabetes Mellitus

Diabetes as a disorder of metabolic disorders of blood sugar poses a huge threat to human health.While type 1 diabetes and type 2 diabetes conventional treatment programs control the stability of blood glucose in vivo by injecting insulin,but injecting insulin cannot simulate the normal release of endogenous insulin in vivo model,which cannot be long-term maintenance of normal blood glucose levels in patients with diabetes.So the researchers hope to find a drug delivery system through the body's blood glucose concentration in real-time monitoring,to release insulin control blood glucose stability and thus avoid hypoglycemic and other side effects.In response to this irritating response to nanocomposites is a recent research hotspot,the response mechanism of different signals is applied to the design of drug delivery systems to apply life science research.Conventional sugar responses include glucose oxidase,glucose binding protein and phenylboronic acid,in which the drug delivery system for insulin delivery can be developed by preparing a benzene-containing boron-containing polymer.However,the sugar response of conventional phenylboronic acid often needs to play a role in the alkaline environment.Therefore,the use of phenylboronic acid-containing nanoparticles under physiological conditions for insulin delivery is an urgent problem to be solved in the study.In this paper,the amphiphilic polymer was prepared by Michael addition reaction of mPEG-1000,and the phenylboronic acid was modified on the surface of the carrier by click reaction.The amphiphilic polymer PEG-PBO was crosslinked with water-soluble polymer PEG-DPA under physiological conditions at the same time,with dopamine with o-diol structure at both ends of polyethylene glycol PEG-1000 to crosslink sugar-responsive nanoparticles.The cyclic nanoparticles formed by have many excellent properties: pKa of 3-carboxy-2-hydroxymethyl-phenylboronic acid is significantly lower than that of conventional phenylboronic acid,and the binding constant with sugar is bigger in the normal physiological pH.Secondly,m PEG can keep the nanoparticles in a good state and not easily precipitate.Finally,groups such as polyethylene glycol and dopamine are easily biodegraded and biologically toxic and have good biocompatibility.In this paper,in vitro experiments were used to evaluate the ability of protein to carry protein and sugar response.Bovine serum albumin was used as model protein,and the loading efficiency of nanoparticles was 21.3%.The prepared nanoparticles can achieve pH dependent protein release.When the drug-loaded nanoparticles were placed in acidic or weakly acidic sugar solution,there was no protein release,and the protein was effectively released when placed in the physiological pH of the sugar solution.The results showed that the sugar response of the nanoparticles under different physiological conditions,and the results showed good sugar response.The release of protein was significantly improved with the increase of sugar concentration.Time dependant protein release was also evaluated.The results showed that the nanoparticles could completely release the fluorescein labeled protein in one hour in a 10 ?g/ul sugar solution.