Investigation On The Drug Delivery System Of Single Walled Carbon Nanotubes Composite Doxorubicin Hydrochloride Liposomes

As a broad-spectrum antitumor drug, Doxorubicin hydrochloride (DOX) has thebetter inhibition effect on all sorts of growth tumor cells, however, the larger hearttoxicity limits its clinical application. Single-walled carbon nanotubes have showngreat potentials both in drug delivery and photo thermal therapy. Because of itsspecific features about huge surface area, large delocalized π bond, uniquetransmembrane ability and the strong capability of absorption at700~1100nmnear-infrared light and heat generation, which make the SWNTs to be a novel targetcarrier materials. A kind of compound nanometer tumor targeting drug deliverysystem (Lys/CNTs-DOX-Lip) was successfully developed, which based on the lipidmaterial wrapped thel carrier and DOX. In this research, we achieved the synergy ofchemotherapy, phototherapy and heat treatment at the same time.We modified the SWNTs with lysine (Lysine,Lys) in the subject first, then theformulation and process of Lys/CNTs-DOX-Lip compound preparation was studied.Through the single factor, the optimal formula was determined: quality ofphospholipids and cholesterol ratio is5:1, drug lipid ratio is1:10, the ultra time is2min, liposomes and carbon nanotubes ratio is2:1.The compound preparation wasstability and black-red suspension liquid, the encapsulation rate was about85.9%using ultra filtration. In the drug delivery system, the final concentrations of carbonnanotubes and doxorubicin was about200μg·ml-1,1mg·ml-1, respectively. Thepharmaceutical properties showed that the particle size and zeta potential of thepreparation was about223±5.9nm and-20±2.3mv. In vitro drug release behaviorwas studied under different pH environment, which indicated that theLys/CNTs-DOX-Lip compound preparation had the characteristics of pH sensitive.To study the pharmacokinetic characteristics of Lys/CNTs-DOX-Lip compoundpreparation in vivo, we took SD rat as the model animal and HPLC was selected todeterminate the concentration of DOX drug in plasma. Compared with the DOXsolution group, Lys/CNTs-DOX-Lip group showed a certain slow-release functionand prolonged the effect of drug in the body, then improved its bioavailability. In order to study the distribution of Lys/CNTs-DOX-Lip compound in S180tumor-bearing mice, we also took HPLC to detect the drug concentration in eachtissue. The results showed that the composite preparation had tumor targeting andreduced the cardiac toxicity at the same time.Taken the relative tumor volume, body weight, daily water intake and daily foodintake as the evaluation index, we studied the influence of Lys/CNTs-DOX-Lip groupand DOX control group on the quality of life in S180mice. To investigate the majororgan toxicity of the delivery systems, we analysised the HE staining result of theheart, liver, spleen, lung, kidney, brain and tumor in a dose range.It showed that thepreparation group had a good anti-tumor effect. Moreover, it did not influence thebody weight and the daily water and food intake, improved the quality of life. Theresults of HE staining indicated that the drug delivery system did not producesignificant tissue toxicity in the dose range.