Research Of Nanostructured Graphene Oxide In Drug Loading And Sustained Release

Graphene oxide(GO)has abundant oxygen functional groups,large specific surface area,good biocompatibility and good disperse ability in water,so it finds great application in the field of biomedicine.However,it agglomerates in phosphate buffer solution(PBS),which deteriorates its drug-loading and release performance.Therefore,it is necessary to improve its dispersive stability in PBS.In order to further increase the specific surface area of GO and tailor the release rate of drug molecules,GO with highly ordered nanostructure was prepared by using lyotropic liquid crystals as soft templates.With GO as the carrier,doxorubicin hydrochloride,5-fluorouracil and docetaxel as model drugs,the drug-loading and sustained-release properties were studied.Lyotropic liquid crystalline(lamellar and hexagonal nanostructure)was constructed by using polyoxyethylene surfactants and GO aqueous dispersions.Lamellar and hexagonal nanostructure were then obtained after removal of template molecules.Polyethyleneglycol(PEG)was used to modify the surface chemistry of GO to improve its dispersive stability in PBS so as to improve the slow-release performance of the drugs.Polarization light microscopy(POM)and low angle x-ray diffraction(low-angle XRD)were used to characterize the nanostructure of liquid crystal phase before and after removal of template,and the defect density of nanostructured GO was analyzed by Raman spectroscopy.UV spectrometry and simulated release test in vitro were used to determine drug loading capacity and drug release performance,scanning electron microscopy(SEM)was used to observe the morphology of the carrier,and contact angle measuring was conducted to analyze the polarity change of samples.The dispersive stability of samples was characterized by UV spectrometry and the change of functional groups before and after grafting PEG into GO was characterized by Fourier transform infrared spectroscopy(FTIR).The main conclusions obtained are as follows:(1)Nanostructured GO was obtained from lyotropic liquid crystalline phase.The highly ordered nanochannels can be used as space for adsorption and diffusion of drug molecules,the layer spacing/pore diameter is related to the chain length of surfactants molecules.(2)The grafting of PEG on GO obviously improved its dispersive stability in PBS,which was related to the decrease of polarity of GO after grafting PEG.It is easier for low polarity substances to disperse well in PBS.After the modification,sustained-release performance of the drugs was improved significantly.The agglomeration of GO was alleviated dramatically,leading to improved diffusion and release ability of drug molecules.(3)Compared with commercial GO,the as-resulted nanostructured GO showed superior drug-loading and sustained-release performance.Moreover,with the increase of pore diameter /layer spacing,the drug amount loaded(mmol/mg)of drug molecules raised.The cumulative release rate decreased when pore diameter /layer spacing decreased,which was related to the non-Fickian diffusion mechanism.Larger pore diameter /layer spacing was beneficial to the adsorption and diffusion of drug molecules,especially those with shorter chain length.(4)Compared with hexagonal nanostructured GO,lamellar nanostructured GO had stronger drug loading ability and higher cumulative drug release rate.It was believed that lamellar structure with weaker steric hindrance was more beneficial to the adsorption and release of drug molecules.(5)The nano-archietecture(lamellar or hexagonal)and pore diameter /layer spacing of GO had significant effects on the drug-carrying and sustained-release properties.A well-designed nanostructure of carriers could provide tailored drugcarrying and sustained-release performance,favorable for the thorough understanding of the drug loading and release mechanism,and the finding of the new path for the practicle application of GO.