The Study On The Preperration And Drug Loading Properties A Of Folater-tageted Nano Grephene Oxide

Objective:To study on the preparation of nano-targeting drug delivery system of graphene oxide with good biocompatibility,then the platinum metal complexes?cisplatin,carboplatin,oxaliplatin,eptaplatin?were slected and loaded on the nano-targeting drug delivery system of graphene oxide respectively,and the loading,release and the vitro anticancer propertise were studied to select the promising grophene oxide drug carrier for platinum metal complexes.Method:1.Graphene oxide?GO?was prepared by the modified Hummer's method,then it was functionalized with the high molecular polymer polyethyleneimine?PEI?,polythylene glycol?PEG?,chitosan?CS?and folic acid?FA?to prepare nano-targeting drug delivery systems with good biocompatibility?GO-PEI-FA,GO-PEG-FA,GO-CS-FA?,then its physical and chemical properties were charectered by Fourier transform infrared?FTIR?,Ultraviolet visible spectrophotometry?UV-Vis?,Scanning electron microscopy?SEM?andX-ray diffraction?XRD?.2.The platinum metal complexes was loaded by ultrasonic oscillation method to the prepare of folate targeted nano graphene oxide drug delivery systems and study on the drug loading and release properties to select the appropriated drug carrier.3.The antitumor effects of carrier and drug delivery system complexes were screened against human liver hepatic stellate cells?LX2?and ovarian cancer cells?SKOV3?by means of MTT assay to investigate its biological safety preliminarily.Results:1.GO,GO-PEI-FA,GO-PEG-FA,GO-CS-FA were successfully prepared and were identified by FTIR,UV-vis,XRD,SEM.2.The saturated Cisplatin-loading rate of GO-PEI-FA,GO-PEG-FA and GO-CS-FA are 36.02?g/mg,21.51?g/mg 33.34?g/mg respectively.The drug release experiments showed that the CDDP release rate of GO-PEI-FA*CDDP,GO-PEG-FA*CDDP,GO-CS-FA*CDDP are 89%,66%,78%respectively.The release rate is higher at pH 5.50 than pH 7.09.3.The nano-targeted graphene oxide on carboplatin drug system?GO-PEI-FA*CBP,GO-PEG-FA*CBP,GO-CS-FA*CBP?were successfully prepared,and the saturated loading rate of carboplatin were 256.32?g/mg,95.61?g/mg,324.4?g/mg respectively.The binding constants were 2.55mL/mg,5.15 mL/mg,and 2.38 mL/mg respectively.The release studies of carboplatinshowedthatthedrugreleaseofGO-PEI-FA*CBP,GO-PEG-FA*CBP,GO-CS-FA*CBP are higher at pH 5.50 than pH 7.09,and the cumulative release rates are above 90%.4.The nano-targeted graphene oxide on oxaliplatin drug systems?GO-PEI-FA*OXP,GO-PEG-FA*OXP,GO-CS-FA*OXP?were successfully prepared.The study on drug loading properties revealed that the oxaliplatin loading rate of GO-PEI-FA,GO-PEG-FA,GO-CS-FA were 337.83?g/mg,113.83?g/mg,59.3163?g/mg,respectively.The binding constants are 1.0530 mL/mg,4.79 mL/mg,4.79 mL/mg respectively.The study on the drug release of GO-PEI-FA*OXP,GO-PEG-FA*OXP,GO-CS-FA*OXP shows that the accumulative drug release rate are 82%,69%,74%at pH 5.50 after 48 hours,while in the pH=7.09environment,the accumulative drug release rate were 79%,34%,55%respectively.5.The nano-targeted graphene oxide loaded eptaplatin drug systems?GO-PEI-FA*EXP,GO-PEG-FA*EXP,GO-CS-FA*EXP?were successfully prepared.The eptaplatin loading rate depended on the drug loading time,the concentration and the surface chemical energy of carriers.The study on drug loading properties revealed that the drug loading rate of GO-PEI-FA,GO-PEG-FA,GO-CS-FA were 80.47?g/mg,103.28?g/mg,164.15?g/mg.The binding constants were 8.12 mL/mg,6.62 mL/mg,4.16 mL/mg.At pH 5.50,the eptaplatin release rate of GO-PEI-FA*EXP,GO-PEG-FA*EBP,GO-CS-FA*EXP were 77%,76%,78%,at pH=7.09 the release rate were 84%,68%,73%respectively.6.The MTT results showed that the IC₅₀value of GO-PEI-FA,GO-PEG-FA,GO-CS-FA on LX2 were 3816.08±8.26?g/mL,4576.66±8.26?g/mL,1541.94±3.08?g/mL respectively.The IC₅₀value of GO-PEI-FA,GO-PEG-FA,GO-CS-FA on SKOV3 were 3816.08±6.14?g/mL,1021.72±7.43?g/mL,6430.15±6.91?g/mL respectively.The IC₅₀value of Cisplatin,GO-PEI-FA*CDDP,GO-PEG-FA*CDDP,GO-CS-FA*CDDP on SKOV3were 3.56±2.11?g/mL,8.64±2.42?g/mL,6.54±2.59?g/mL,8.08±4.50?g/mL.The IC₅₀value of carboplatin,GO-PEI-FA*CBP,GO-PEG-FA*CBP,GO-CS-FA*CBP on SKOV3were 17.62±7.10?g/mL,52.87±11.16?g/mL,52.24±2.92?g/mL,48.64±4.71?g/mL.The IC₅₀value of oxaplatin,GO-PEI-FA*OXP,GO-PEG-FA*OXP,GO-CS-FA*OXP on SKOV3 were64.31±5.42?g/mL,1403.85±4.77?g/mL,967.43±3.08?g/mL,1511.85±8.43?g/mL.The IC₅₀value of eptaplatin,GO-PEI-FA*EXP,GO-PEG-FA*EXP,GO-CS-FA*EXP on SKOV3 were 27.25±2.21?g/mL,41.80±3.70?g/mL,63.54±5.85?g/mL,43.55±4.36?g/mL.Conclusions:1.graphene oxide was prepared by the ultrasonic-assisted Hummer method.2.The research on CDDP loading showed that GO-PEI-FA and GO-CS-FA were the good carriers of loading CDDP on drug delivery system.3.The research on CBP loading showed that GO-PEI-FA and GO-CS-FA had higher drug loading rate and more suitable combining ability and they were good as carriers of CBP.4.The research on OXP loading showed that GO-PEI-FA had higher drug loading rate and more suitable combining ability and it was good as carriers of OXP.5.The research on EXP loading showed that GO-PEG-FA and GO-CS-FA had higher drug loading rate and more suitable combining ability and they were good as carriers of EXP.3.GO-PEI-FA GO-PEG-FA,GO-CS-FA nanoparticles,have low toxicity,it could be used as a drug carrier.The anticancer effect of platinum anticancer drugs and drug delivery system to platinum is weaker than the corresponding positive drug,the specific mechanisms stil need a further study.