羟基喜树碱脂质体的制备及其抗肿瘤效果的评价-东南大学学报医学版

羟基喜树碱脂质体的制备及其抗肿瘤效果的评价

作者：陈文忠¹ 庄翌¹ 郝翌¹ 陈家英² 腾德义² 段晓波² 梅胜尧² 杜颖³ 陈宝安³

单位：1. 南京绿叶制药有限公司, 江苏南京 210061;
2. 江苏省药物研究所, 江苏南京 210009;
3. 东南大学附属中大医院血液科, 江苏南京 210009

分类号：R979.1

出版年·卷·期（页码）：2020·39·第四期（407-412）

摘要：

目的：制备羟基喜树碱脂质体，并观察其对小鼠肝癌H₂₂及肉瘤S₁₈₀实体瘤的抑瘤作用。方法：薄膜分散法制备羟基喜树碱脂质体，并对其粒径等理化性质进行表征；昆明小鼠分别于右腋下皮下接种肝癌H₂₂及肉瘤S₁₈₀瘤种，隔日静脉注射给药1次，共给药3次，末次给药后第5天取血涂片进行白细胞计数，并将动物处死，剥离皮下肿瘤并称重，计算抑瘤率。结果：羟基喜树碱脂质体平均粒径为357 nm，包封率大于93%，活性δ内酯环形式大于98%。羟基喜树碱脂质体对小鼠移植性肿瘤H₂₂肝癌和S₁₈₀肉瘤均有明显抑制作用，与同等剂量（3 mg·kg^-1）市售羟基喜树碱注射液比较，抗肿瘤作用差异有统计学意义（P<0.001）；各给药组（除小剂量组）都有不同程度的降低白细胞的作用，与空白对照组比较差异有统计学意义（P<0.01）；各剂量给药组未见对骨髓细胞有抑制作用。结论：羟基喜树碱脂质体可抑制肿瘤生长，同时也不增加羟基喜树碱的毒性。

Objective: To prepare Hydroxycamptothecin liposome and observe its anti-tumor effect on H₂₂ hepatoma and S₁₈₀ sarcoma animal models in mice. Methods: Hydroxycamptothecin liposome was prepared usingfilm-dispersion method, and its characteristic such as particle size, was studied. The H₂₂ hepatoma and S₁₈₀ sarcoma models were established in KM mice. They were injected intravenously every other day for three times. On the fifth day after treatment, the animals were killed, and blood samples were collected to count white blood cells, and the subcutaneous sarcoma were separated and weighted. Tumor inhibition rate were calculated. Results: The size of the Hydroxycamptothecin liposome was 357 nm. The encapsulation efficiency was more than 93%, and the ratio of active form was more than 98%. Hydroxycamptothecin liposome could inhibit the growth of both H₂₂ hepatoma and S₁₈₀ sarcoma tumor, At the same dose, the differences were statistically significant between Hydroxycamptothecin liposome groups and Hydroxycamptothecin injection(P<0.001). White blood cells were reduced to varying degrees in all treatment groups and the differences were statistically significant between control group and treatment groups. Conclusion: Hydroxycamptothecin liposome con inhibit the growth of tumour.

参考文献：

[1] ZHANG W,LI M,DU W,et al.Tissue Distribution and Anti-Lung Cancer E_ect of 10-Hydroxycamptothecin Combined with Platycodonis Radix and Glycyrrhizae Radix ET Rhizoma[J].Molecules,2019,24(11):2068.
[2] WU Z,LI S,CAI Y,et al.Synergistic action of doxorubicin and 7-Ethyl-10-hydroxycamptothecin polyphosphorylcholine polymer prodrug[J].Colloids Surf B Biointerfaces,2020,189:110741.
[3] 杨小飞,张鹏飞.华蟾素胶囊联合羟基喜树碱对中晚期食管癌疼痛患者的疗效分析[J].现代医学,2019,47(11):1333-1336.
[4] 胥彬.拓朴酶Ⅰ抑制剂羟基喜树碱类药物研究进展[M].2020全国肿瘤学术大会论文集,2002:2.
[5] 张力,李苏,管忠震,等.羟基喜树碱Ⅰ期药代动力学及人体耐受性临床研究[J].癌症,2001,20(12):1391-1395.
[6] SCOTT D O,BINDRA D S,STELLA V J.Plasma pharmacokinetics of lactone and carboxylate forms of 20(S)-camptothecin in anesthetized rats[J].Pharm Res,1993,10(10):1451-1457.
[7] SHUANG R,WANG M,MAO J,et al.Pharmacokinetics of 10-hydroxycamptothecin-tetrandrine liposome complexes in rat by a simple and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry[J].J Sep Sci,2020,43(3):569-576.
[8] SASAKI Y,YOSHIDA Y,K SUDOH K,et al.Pharmacological correlation between total drug concentration and lactones of CPT-11 and SN-38 in patients treated with CPT-11[J].Jpn J Cancer Res,1995,86:111-116.
[9] TARDI P,CHOICE E,MASIN D,et al.Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and human xenograft models[J].Cancer Res,2000,60(13):3389-3393.
[10] THOMAS G BURKE.Formulation and evaluation of bilayer versus core-loaded liposomal camptothecins[M].2001 ASCO Annual Meeting,2001:13.
[11] 黄洁,章真,何小芳,等.肿瘤靶向性生物膜纳米载药系统的研究进展[J].东南大学学报(医学版),2017,36(5):868-871.

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