Preparation And Drug-loading Properities Of PH-sensitive Micelles From Amphiphilic Polymers

In recent years,the administration of subcutaneous intravenous injection for diabetes treatment has many defects,oral administration of insulin has received extensive attention due to its various advantages.However,during the oral administration,insulin is easily inactivated by enzymatic degradation in the gastrointestinal tract,and its have poor targeting delivery and low bioavailability.These bottlenecks obviously limit the oral administration of insulin.The intelligent and efficient nano drug delivery carrier can solve the problems of oral administration of insulin,especially the stimuli-responsive polymer carrier material,such as pH-responsive insulin polymer nanocarrier,which has attracted much attention.According to the pH change of the environment in the gastrointestinal tract,a series of pH-responsive amphiphilic polymers were synthesized in this work.The dialysis method was used to realize the self-assembly of the polymer to form micelles which loaded insulin.A drug nanomicelle system in which polymethacrylic acid(PMAA)is selected as a pH response block.○1 P(PLAMA-co-MAA)-b-PPEGMA.The amphiphilic block copolymer is obtained by ROP polymerization of ARGET ATRP of methacrylic acid monomer and aliphatic lactone,and the hydrophobic block is a ring-opening polymer of hydroxyethyl methacrylate and lactide.The CMC value of the material is 1.387-4.037 mg/L,and a stable micelle structure can be formed at a low concentration.The polymer-loaded micelles have small particle size,spherical morphology and good biocompatibility,drug-loaded micelles in the simulated gastric fluid environment(pH=1.2),the cumulative release of insulin for 10 h was about 25%;while in the simulated intestinal fluid(pH=7.4),the cumulative release was up to 70% at 10 h,and the controlled release of micelles performance well.At the same time,this work has optimized the micelle preparation process.○2 Chol-g-P(HEMA-co-MAA)-b-PPEGMA.The amphiphilic polymeric material having a high cholesterol grafting density is obtained by the alcoholysis reaction of a polyhydroxyethyl methacrylate block with cholesterol chloroformate.The drug-loaded micelles have a particle size of 200-300 nm.In simulated gastric juice,insulin release is slow,and the cumulative release in 10 h is less than 20%,which is beneficial to reduce the leakage of drug loaded in the micelle core.In the simulated intestinal fluid environment,the insulin release rate is accelerated,and the cumulative release rate is higher than 90%,indicating that the controlled release properties of insulin in this micellar system have been improved relative to the polymer P(PLAMA-co-MAA)-b-PPEGMA micellar system.At the same time,the process and mechanism of micelle formation were discussed from the perspective of dissipative particle dynamics simulation.pH-responsive polymer micelles,as insulin nano-reporting carriers,utilize the changes in the gastrointestinal microenvironment to achieve controlled release of drugs during oral administration of insulin,it will have potential applications in oral insulin preparations.