Construction And Evaluation Of Brucine-loaded Ga Mediated Breakable Intracellular Nanoscale Drug Delivery System

Objective:Construction on GA mediated breakable intracellular nanoscale drug delivery carrier,Evaluation of intracellular breakage and safety;using brucine as a model drug,Construction on brucine-loaded GA mediated breakable intracellular nanoscale drug delivery system by nano drug loading technology,optimize processes and prescriptions and characterize it.In order to achieve the goal of improving the efficacy of drug delivery to cells,it provides a basis for the synergies in the later period.Methods:Preparation of GA mediated breakable intracellular nanoscale drug delivery carrier by amide reaction and esterification reaction,optimizition the preparation condition used single factor method,the structures were identified by FT-IR and 1H-NMR.The intracellular environment was simulated to verify the fragmentation of the drug delivery.Using UV for the stability evaluation of nano drug delivery system;the hemocompatibility of the drug delivery was evaluated by the hemolysis test;SMMC-7721 liver cancer cell as model,the cytotoxicity of drug delivery carrier was investigated by MTT assay.HPLC method for brucine content determination,comparative method screening preparation method of the construction on GA mediated breakable intracellular nanoscale drug delivery system;optimizition the technology and prescription used single factor method combined with Central Composite Design Response Surface,determination of particle size,PDI,Zeta potential with Malvem laser particle size analyzer,particle morphology was observed by TEM,DSC was used to investigate the existence of brucine in the nanoscale delivery system.Results:1.Optimized preparation conditions of GA mediated breakable intracellular nanoscale drug delivery carrier,FT-IR,1H-NMR etc.detection profiles show amide and ester bonds in the reaction polymer,it proves connection of GA,PEG,DTDP,GMS.The constructed drug delivery carrier can break in a simulated intracellular reducing environment and has a certain restoring response.2.Stability test shows the critical flocculating concentration of the nanoscale drug delivery system is 0.7 mol/L.Hemolytic experiment shows that GPSG and PSG polymer on the concentration of 5～1000μg/mL,no hemolysis occurred within 3h,and the hemolytic rate was less than 5%.MTT experimental results show that when the concentration of PSG polymer was between 5 and 1000μg/mL,the cell survival rate was higher than 80%within 72 hours.After the introduction of GA,the cell survival rate of GPSG polymer decreased,and the cells had a certain inhibitory effect.3.Used the methods of the ultrasound emulsification solvent to prepare the brucine-loaded GA mediated breakable intracellular nanoscale drug delivery system.Optimized prescription:the dosage of GPSG polymer was 10mg,lecithin was 8mg,oleic acid was 20mg,organic phase and water phase ratio was 0.37,F68 concentration was 0.12%,and the drug dosage was 1.02 mg.The optimized nanoparticles were light blue emulsion.the average particle size was(119.24± 1.79)nm,PDI was 0.187±0.005,Zeta potential was(-23.88±0.67)mV,encapsulation efficiency was(69.33±1.66)%,drug loading was(1.36±0.03)%.TEM showed that brucine-loaded GA mediated breakable intracellular nanoscale drug delivery system is a complete spheroidal particle,uniform size distribution,basically consistent with the particle size measured by laser particle size analyzer;DSC showed that brucine existed as molecular or amorphous state in the drug delivery system.Conclusion:This topic has been successfully constructed GA mediated breakable intracellular nanoscale drug delivery carrier,in intracellular environment can break,good blood compatibility.Using nanotechnology,the model drug brucine which is an effective model for anti-hepatocellular carcinoma,is encapsulated by a constructed drug delivery carrier,the prepared nanoparticles have a small particle size and PDI,higher encapsulation efficiency,complete spherical spheres,it shows that the drug delivery carrier constructed has good drug loading effect.This topic provides a new idea for the development of intracellular nano drug delivery carriers,to provide a scientific basis for the establishment of an active liver-targeted nano drug delivery system technology platform,receptor-mediated Chinese medicine ingredients and therapeutic drugs produce pharmacological synergies that promote the continuous innovation of traditional Chinese medicine theories.