Research Of Preparation And Drug Release Of Doxorubicin/Curcumin Degradable Drug Delivery Systems

The functional degradable drug delivery systems have become the key researching content in the field of pharmacy with the development of the biomedicine.How to control the particle size of carriers,to improve the drug load capacity and realize the multifunction system are the main development direction of drug carriers in the future.The functional drug carrier system is being transformed to the direction of the multimaterial,dual-drugs and multiple-methods from traditional single-material,single-drug and single-method.The multifunctional composite materials have the characters of magnetism,pH-responsive,temperature response and drug sustained release.The disadvantages of low utilization rate and poor selectivity are avoided effectively.The drug-loading efficiency and release efficiency of carriers are optimized.The paper researched on the dual loading materials and the dual drugs while a series of anti-cancer systems loaded with drugs were synthesized.Meanwhile,the constituent and the performance of the products were analyzed systematically.The magnetic carriers loaded with dual anticancer drugs were prepared by the coprecipitation and the emulsion-solvent evaporation methods while the degradable material of polylactic acid（PLA）was adopted as carrier material,the doxorubicin（DOX）and the curcumin（Cur）were selected as anticancer drug template and the Fe₃O₄ magnetite nanoparticle was chosen as magnetic material.The experimental conditions were optimized and the best synthesis conditions were:the PLA（0.6 g）,the relative molecular mass of PLA（50 KDa）,the concentration of polyvinyl alcohol（2%）,the stirring rate（1500 r/min）and the ultrasonic power（200 W）.The hydrophilic doxorubicin and the hydrophobic curcumin were loaded in the aqueous phase and the oil phase respectively.The coexisting system of anticancer drug and magnetic material was established.The carrier maintained the magnetic content of 27.9 emu·g^-11 and had favourable thermostability.The release time and release rate of doxorubicin were 50 h and 64.8%respectively.The total release time and release rate of curcumin reached 112 h and 88.7%respectively.The pH of dissolve medium reduced with the hydrolysis of the PLA and the preserving rate was 80.3%in 45 d.ThePLGA@CS@PAsystemloadedwithdrugswerepreparedbythe emulsion-solvent evaporation and the covalentcross-linkedmethodswhile the polylactic-co-glycolic acid（PLGA）and chitosan（CS）were adopted as coating materials,the Cur was used as drug and the phytic acid（PA）was selected as modifying material.Cur and PA have antitumor activity simultaneously.The system provided a synergetic platform of liposoluble anticancer drugs and anti-cancer materials.The best experimental conditions were:the ratio of PLGA:CS（5:1）,the concentration of PLGA(60 mg.mL^-1),the concentration of polyvinyl alcohol（2%）,the concentration of chitosan（1%）,the ultrasonic power（200 W）,the stirring rate（1500 r/min）,the ratio of O:W ratio（1:2）,the ultrasonic time（3 min）and the drug-loading rate and the encapsulation efficiency of microspheres were 8.9%and 73.4%respectively.The drug release capacity was increased with the reduction of pH and the increase of the temperature.The total release ratio of carrier drugs was 89.8%in the conditions of pH=5 and 37?C within 26 d,while the drug-release performance of pure drug and the drug with carriers was compared,The double-walled long-acting system loaded with dual anticancer drugs was synthesized using W1/O1/O2/W2 emulsion-solvent evaporation method and the thermostability was excellent,while the two kinds of degradable material（PLGA50:50 and PLGA75:25）were chosen as carriers,the DOX and Cur were adopted as loading drugs.The DOX was encapsulated in the internal phase（W1）and the Cur was incorporated into the inner oleic phase（O1）.The release time was prolonged due to the double protections of the internal and the outer oleic phases.The total release time of DOX was 34 d,the release ratio was 81.3%.The accumulate release time of Cur was 39 d,the release ratio was 82.5%.The mechanism of degradation and the process were analyzed about the drug carriers,the effect on drug release was studied about the degradation of PLGA.The system gradually degraded within 39 d and the preserving rate of microspheres was 76.3%with the reduction of the pH in the dissolution medium.Combining with the in-situ method,the dual anticancer drug carrier system of Fe₃O₄@ZIF-8@PA was prepared,which has the magnetic response and the pH response,while the zeolite imidazate framework material（ZIF-8）was selected as carrier,the Fe₃O₄magnetite nanoparticle was adopted as substrate material,the PA was chosen as modified materials and the hydrosoluble DOX was used as template drug.The corn（Fe₃O₄）of carriers was encapsulated by ZIF-8 and PA layer-by-layer.This system showed high magnetite content of 35.5 emu·g^-1and maintained well thermostability.The accumulated release ratio was 39.8%and 82.8%respectively in the conditions of pH=7.4 and pH=5.The cell viability experiment showed that the DOX and the PA in the carriers have synergistic therapeutic effect on tumour cells.