Preparation Of Glucose-Responsive Release Silk Fibroin Microneedles

Silk fibroin is a natural protein composed of natural amino acids,has good biocompatibility and is widely used in drug release,tissue engineering,biomedicine and other fields.In this paper,silk fibroin as raw materials to develop a glucose-responsive microneedles,for controlled release of insulin.In this paper,the isoelectric point of silk fibroin was modified from 4.2 to neutral or alkaline by grafting small positively charged molecules on silk fibroin,the silk fibroin molecules are changed from negatively charged to positively charged,thereby obtaining silk fibroin molecules sensitive to acidic pH.Glucose oxidase is then added as a glucose-sensitive reagent to silk fibroin microneedles to catalyze the oxidation of glucose to form gluconic acid,reduce the local pH value in the microneedles,further change the swelling of the microneedles,and accelerate insulin as the glucose concentration in the outside world increases.The purpose of the release rate is to achieve the controlled release of insulin at different blood glucose concentrations.On this basis,a glucose-responsive silk fibroin drug release microneedle was prepared in this paper,and the law of drug release in vivo and in vitro was discussed.In vitro experiments,fluorescein isothiocyanate(FITC)-labeled insulin was used as a model drug,and rabbit skin was used to simulate human skin to complete the transdermal drug release experiment.The microneedle has excellent mechanical properties,can penetrate into the skin of rabbits,and maintain the shape of the microneedles.The release data show that the microneedle has pH sensitivity and glucose sensitivity,the drug release rate is different in different pH buffer solutions,and the drug is released rapidly under low pH conditions;the drug is released under neutral or alkaline conditions is significantly reduced.The drug release rate is different in physiological saline with different glucose concentrations.The drug release rate is fast under high glucose concentration conditions;the drug release rate is reduced under low glucose concentration conditions.In vivo experiments,human recombinant insulin was used as a model drug,and SD rats were used as model animals to complete the drug release experiment in vivo.The results show that the microneedles are blood glucose responsive,and insulin is rapidly released in diabetic rats.The results of microneedle patch used to treat diabetic rats showed that the blood glucose levels in diabetic rats decreased significantly before meals,and the blood glucose levels in rats increased and then decreased after meals;in normal rats,the blood glucose values remained basically after meals smooth.This shows that the microneedles achieve controlled release of insulin at different blood glucose concentrations,and provide a new method for research and treatment of diabetes.