Abstract:

ObjectiveTo compare the tumor suppressive efficacy of paclitaxel liposome through intratumoral injection in mice H22 xenograft tumor models with that through intravenous injection and discuss the possibility of applying microsphere drug agents in the intratumoral chemotherapy. MethodsH22 subcutaneous xenograft tumor models were established in ICR mice and distributed randomly into 3 groups with intratumoral injection of 5％ glucose solution （IT-GS， control group）， intravenous injection of paclitaxel liposome （IV-PL） and intratumoral injection of paclitaxel liposome （IT-PL）. When tumor diameter reached 10mm at 10⁺ days posttreatment， intratumoral injection guided by ultrasonography and intravenous injection through tail vein were given separately once a week in the following two weeks. The in vivo nearinfrared fluorescence imaging was used to indicate the drug distribution in mice within 24h after administration. The paclitaxel liposome with concentration of 3mg／ml was administered at a dose of 75mg／kg. Adverse effect and tumor volume change were observed and recorded every other day. Mice were executed on the 14th day of treatment. The tumors were excised, weighted, embedded in paraffin and then stained with H&E for futher pathologic analysis. ResultsIncreased echogenicity could be detected by ultrasonography when paclitaxel liposome was injected intratumorally， ensuring that the drug distributed in the tumor. The in vivo nearinfrared fluorescence imaging displayed a sustained high drug concentration confined in tumor for 24 hours after intratumoral injection， while a gradually increasing and relatively low concentration of drug in tumor after intravenous injection. The tumor regression rates of ITPL group and IV-PL group were 95.0％ and 56.1％ with statistical significance（P＜0.05）. The following pathologic examination under microscope revealed that densely growing malignant tumor cells were found in control group while in ITPL group there was lipid deposition around and inside the tumor and a relatively small amount of residual tumor cells could be found on the edge. Nevertheless， the vitality of the mice in ITPL group was the best among the 3 groups. No obvious diabrosis or erosion of subcutaneous tissues and overall adverse effect were observed in ITPL group. ConclusionThese results indicate that the intratumoral injection of paclitaxel liposome would be a safe and effective method in the treatment of local solid tumors.