Preparation And Evaluation Of Hepatic Targeted Oxide Graphene Carrier For Transferring Rice Platinum

We prepared and evaluated a novel nano device which based on graphene oxide(GO) loading miriplatin(MP). This nano device has characteristics of liver targeting, long circulating and being given intravenously. To achieve these goals, we chemically modified our carrier materials. Glycyrrhetinic acid(GA) was bridged to the surface of GO via a terminal chemical modified polyethylene glycol(NH2-PEG-COOH) to form a triblock copolymer GA-PEG-GO(GPG). GA is a ligand which targets to liver and PEG can prolong circulation time. We used Dioleoyl Phosphoethanolamine(DOPE) and(2, 3-Dioleoyloxy-propyl)-trimethylammonium(DOTAP) to prepare liposome and package water-insoluble drug MP. Amino group of DOPE and carboxy group of 1-Pyrenebutyric acid(PBA) are coupled by an amide linkage. The π-π interaction will be formed between phenanthrene of PBA and carbon ring of GO so that liposome can combine with GO. The chemical structure of polymers was identified by mass spectrometry, 1H NMR spectra or FT-IR spectra. Morphological structure of liposome was observed by transmission electron microscope(TEM). According to the fluorescence quenching effect of GO to speculate the combination between liposome and GO. The partical size and zeta potential of complex were measured by Malvern Zetasizer Nano instrument. Free MP was separated from liposome by 0.22 μm filter membrane and encapsulation efficiency(EE) of MP was determined by HPLC. The developed method was studied by a series of validation tests. Results indicated that we have successfully synthesized our target polymers. The prepared liposome is spherical in shape and present lipid bilayer and fingerprint structure. The decrease of liposome fluorescence intensity indicated that the liposome was successfully conjugated with GO. The average size of nano device is 251.1 nm and average potential is +35.7 m V. Methodological validation showed that the developed filter membrane-HPLC method is precise and feasible for the determination of EE. The encapsulation efficiency(EE) of MP is 87.62%. Drug distribution in tumor-bearing mice results showed that the prepared nano device have properties of liver targeting and tumor targeting.