Construction And Activity Evaluation Of Intelligent Responsive Nano Drug Delivery System For Anti-Inflammatory Single Drug

Inflammatory bowel disease(IBD)excessively producing reactive oxygen species(ROS)and lower pH value constitute a unique physiological environment of inflammatory tissue.Using patholodical tissue microenvironment to design an intelligent drug delivery system was an effective way to achieve targeted disease treatment and enhance the effectiveness of drug treatment,and it was also a hot research field among scientists.This topic was based on the characteristics of high reactive oxygen species(ROS)content in the microenvironment of inflammatory tissues and a lower pH than normal tissues.The pH/ROS dual responsive nanocarriers based on aryl borate was designed and constructed by using inflammatory tissues as targets,also designing intelligent responsive molecular and using targeted molecular modification and nanocarrier self-assembly methods.First of all,a low molecule weight NBC of aryl boronate ester corresponding to ROS was synthesized,and then it was coupled to the amino group of the chitosan derivative of the macromolecular skeleton through the active group.After that the drug quercetin or berberine derivative(BBR-1)with anti-inflammatory effect was connected by the borate ester to form the hydrophobic end of the macromolecular skeleton which have the pH responsive.Based on ethylene glycol chitosan or carboxymethyl chitosan,a macromolecular skeleton containing hydrophilic/hydrophobic ends were prepared,and nanomicells were formed by self-assembled in an oil-in water environment.Then the ethylene glycol chitosan-boric acid was constructed.Ester polymer grafted quercetin nanomicelles(GC-B-Que)and carboxymethyl chitosan-borate polymer grafted berberine nanomicelles(OC-B-BBR)two systems.Nuclear magnetic,molecular weight,particle size,zeta potential,scanning electron microscopy,stability and other tests were carried out on the nanocarriers.The results showed that the two nanocarriers were nearly spherical particles with a particle size of 100?130 nm,and the particle size distribution was uniform.Finally,colon length,spleen index,weight change,DAI score and other indicators were used to evaluate the therapeutic effects of GC-B-Que and berberine derivatives(BBR-1)on inflammatory bowel disease in mice.The experimental results showed that GC-B-Que drug-loaded nanomicelles and BBR-1 can effectively treat colitis in mice.The drug tissue distribution results show that GC-B-Que nanomicelles can increase the content of quercetin in the lesions,thereby increasing the therapeutic effect of GC-B-Que nanocarriers on inflammatory bowel disease in mice which shows the feasibility of using it to construct intelligent responsive nanocarrier materials for targeted delivery.In summary,we had prepared a novel pH/ROS intelligent dual-responsive nanocarrier and targeted delivery of IBD therapeutic drugs through the inflammatory microenvironment,so that the drugs can be controlled and released in the inflammatory tissues,improving the efficacy of IBD therapeutic drugs and security.The special structure of the borate ester combined with catechol drugs can also be used for the delivery of other catechol drugs,providing a new idea for the construction of drug delivery systems.