Preparation And Drug-loading Performance Study Of Reduction-sensitive Nano-micelle

The polymer micelle,has drawn people's attentiton depend on it's special core-shell structure,lower critical micelle concentration and endurance of fluid resistance,improving the solubility of hydrophobic drugs and extending the cycle time of micelle in the blood.According to the difference between tumor and normal tissues,people mainly made use of natural or synthetic materials to achieve the purpose of loading drug by physical adsorption,chemical bonding in different ways.Drugs were released after transportted to tumor site,exerting drug effectiveness under a series of stimulus,such as,GSH,pH,temperature,ionic strength,magnetic,optical and so on.The present paper designed two kinds of reduction-sensitive drug-loaded nano-micelle drug micelle and studied their performance of drug-loading according to the concentration difference of GSH between tumor and normal tissue.The main research content was as follows:?1?Designed connectted hydrophilic methoxy polyethylene glycol?mPEG?with hydrophobic cetyl alcohol by diselenide bonds to get amphiphilic polymer mPEG-Se-Se-C₁₆.The structure were characterized by Raman,FT-IR and¹H NMR.The polymer was dissolved in DMSO with DOX,and then formed nano-micelle by self-assembly in the water.It turned out that the micelle with a size of 198±5 nm and low polydispersity index of 0.32.The envelopment rate of DOX-loaded nano-micelle was51.92%and drug-loading rate was 9.01%.In vitro release profiles showed that the DOX release rate and amount in pH 7.4 with 0.01 M GSH was faster and higher which drug release around 92%after 7.5 h.But,there was only little release in PBS.Cytotoxicity test against HeLa celles showed that the IC₅₀ was figured out to be 3.73?g/mL,but for COS-7,there was more than 60%were live.?2?Synthesised amphiphilic polymer micelle with selenium-sulfur bond,which self-assembly in water formed micelle as the ball with a size of 127±9 nm and low polydispersity index of 0.13.The critical micelle concentration was 0.03 mg/mL.The DOX-loaded nano-micelle has envelopment rate of 53.16%and drug loading rate of13.41%.The system was used for simulating the tumor microenvironment of drug release,the results showed that drug release rate was almost 100%when 50 h.But,there was noly39%release in PBS.Cytotoxicity test against HeLa celles showed that the IC₅₀ was figured out to be 1.03?g/mL,but for COS-7,there was more than 80%were live.Compared two systems,nano-micelle particle size were all between 100²00 nm and sent DOX to lesion location with the size advantage by enhancing permeability and retention effect.The above two kinds of DOX-loaded nano-micelle not only can rapidly disintegrate to release DOX in GSH environment,but also effectively inhibit the growth of HeLa cells,and DOX-free nano-micelle has unconspicuous cytotoxicity.Diselenide bonds system realized the drug-loading nano micelle structure rapidly disintegrating in the GSH environment and released DOX quickly and completely.But selenium-sulfur bonds system reduced the leak of DOX in transit and increased the utilization ratio of the DOX.Selenium-sulfur system has higher drug-loading rate coating rate,smaller size and less side effects to COS-7 than diselenide system.