Preparation、Pharmacokinetics And Tissue Distribution Of MWCNTs-PTX

Carbon Nanotubes（CNTs）are considered to be a good nanomaterial because of their unique physical and chemical properties.CNTs have large specific surface area,which is suitable for drug loading and administration,and provides a carrier platform for the transfer of biomolecules such as DNA,RNA,protein and so on.However,due to the strong hydrophobicity and low biocompatibility of CNTs,their application in medicine is limited.Therefore,we proposed to use DSPE-PEG non-covalent modification of carboxylated multi-walled carbon nanotubes（MWCNTs-COOH）to improve their biocompatibility.Furthermore,Paclitaxel（PTX）,an insoluble antitumor drug,was loaded on the modified MWCNTs-COOH to study its pharmacokinetics characteristics and tissue distribution in animals after intravenous injection.In this paper,PEG functionalized multi-walled carbon nanotubes（MWCNTs-PEG）were prepared by probe ultrasonic.The products were characterized by TEM,FTIR and ¹H-NMR.The results showed that DSPE-PEG had been bound to carbon nanotubes.The hemolysis test showed that the hemolysis rate of MWCNTs-PEG group was less than 5%,which was significantly lower than that in MWCNTs-COOH group.Compared with the control group,the plasma recalcification time was delayed in the different concentrations of MWCNTs-COOH and MWCNTs-PEG.The OD value of MWCNTS-PEG was obviously lower than that of MWCNTs-COOH group.Under the condition of controlling the preparation temperature,a certain amount of MWCNTs-PEG carrier and anhydrous ethanol was added,and the ratio of drug PTX to carrier was 2:1.After 2 h of probe ultrasound,the mixture was evaporated in 40^oC water bath under the blow of nitrogen,then added ultra-pure water,dispersed by probe ultrasound for2 h.the product was centrifuged at 8000 r·min^-1 for 10 min.The drug loading rate of PTX-MWCNTs-PEG complex was over 60%.The release curve in vitro was determined with reversed-phase dialysis method and the drug release curve was fitted by different models.The results showed that the drug was released according to Higuchi model.A method has been established for the determination of PTX in rat plasma by HPLC and studying the pharmacokinetics of PTX-MWCNTs-PEG complex and PTX control solution after intravenous injection in rats.Blood samples were collected at 0.083,0.17,0.25,0.5,1,2,4,6,8,10 h after administration of 8 mg·kg^-1（PTX）intravenously.Methyl tert-butyl ether（MTBE）was used to precipitate protein in samples after the addition of internal standard,and drug concentrations at each time were analyzed by HPLC.Draw the drug-time curve.As a result,the main pharmacokinetic parameters analyzed by DAS 2.0 were showen as follows:PTX-MWCNTS-PEG:AUC_（0-t）=42.587±1.629 mg·h·mL^-1,t_1/2β=1.16±0.24h,CL=0.418±0.015 L·h·kg^-1;PTX:AUC_（0-t）=25.705±0.685 mg·h·mL^-1,t_1/2β=0.834±0.103 h,CL=0.66±0.016 L·h·kg^-1.The results showed that the complex could improve the bioavailability of PTX,slow down the rate of drug elimination and prolong the action time of PTX.PTX in tissue samples has been determined by HPLC,according to which PTX tissue distribution of PTX-MWCNTs-PEG in mice were studied.PTX-MWCNTs-PEG and PTX control solution were injected intravenously at the dose of 8 mg·kg^-1（PTX）,the mice were sacrificed at0.5,2,4,8 h,and their heart,liver,spleen,lung and kidney organs were removed quickly.Methyl tert-butyl ether（MTBE）was used to precipitate protein in samples after the addition of internal standard,and then concentrations were detected by HPLC.The results showed that the drug content of the complex was relatively high in the liver and spleen of mice after tail vein injection.