载阿霉素胶束抗胶质瘤体外实验研究

杨  达
资中县人民医院

摘要


目的:制备了具有二硫键响应的高分子MPEG-SS-PCL,以此为载体,制备了安全有效的载阿霉素纳米
颗粒,评价了其对U87胶质瘤细胞的抗肿瘤效果。方法:将MPEG-COOH和胱胺通过EDC缩合得到MPEG-SS-NH2,再开环己内酯得到含有二硫键的两嵌段共聚物MPEG-SS-PCL,之后,通过常规的溶剂挥发法制备了载阿霉
素的纳米颗粒,评价了胶束的二硫键响应性能,紫外方法测定了胶束的载药率,体外观察了载药胶束的释放效率及
对U87胶质瘤细胞的抑制效果,最后采用Alamar Blue法检测纳米胶束对胶质瘤U87的细胞毒性作用。结果:载阿霉
素胶束形态均一,粒径小于50nm。在体外释放实验中,在高浓度谷胱甘肽(GSH)条件下,能快速释药。载药还
原响应胶束在胶质瘤细胞中也能较好的响应,并很好的释放出阿霉素,进一步的细胞毒性试验中,也证实了还原响
应胶束对胶质瘤细胞U87有很好的杀灭作用,其IC50值和裸药没有太大差异,而无响应的载药胶束则对U87没有太
大的杀灭作用。结论:应用具有二硫键响应的高分MPEG-SS-PCL能很好的包载阿霉素制备成胶束,因为粒径小于
50nm,能穿过血脑屏障。该载药胶束有很好的还原响应,体外试验中,该载药胶束在U87胶质瘤细胞能很好的响应
并释放出药物,同时,还原响应胶束对U87细胞有很好的治疗作用。

关键词


阿霉素;胶束;胶质瘤

全文:

PDF


参考


[1]Wang, Y. and T. Jiang, Understanding high grade

glioma: molecular mechanism, therapy and comprehensive

management. Cancer Lett, 2013. 331(2): p. 139-46.

[2]Talibi, S.S., B. Aweid, and O. Aweid, Prospective

therapies for high-grade glial tumours: A literature review.

Ann Med Surg (Lond), 2014. 3(3): p. 55-9.

[3]Farheen, M., et al., Harnessing Folate-Functionalized

Nasal Delivery of Dox-Erlo-Loaded Biopolymeric

Nanoparticles in Cancer Treatment: Development,

Optimization, Characterization, and Biodistribution Analysis.

Pharmaceuticals (Basel), 2023. 16(2).

[4]Madani, F., et al., Polymeric nanoparticles for

drug delivery in glioblastoma: State of the art and future

perspectives. J Control Release, 2022. 349: p. 649-661.

[5]姚鹏,et al.,跨血脑屏障复合功能纳米载体系统

的构建.中国医学科学院学报,2006.28(4):p.481-485.

[6]周宓and王志强,跨血脑屏障药物转运的研究进

展.生命科学研究,2009.13(4):p.370-376.

[7]曹远东and章龙珍,血脑屏障对颅内肿瘤综合

治疗影响的研究进展.徐州医学院学报,2005.25(3):

p.267-270.

[8]Allhenn, D., M.A. Boushehri, and A. Lamprecht,

Drug delivery strategies for the treatment of malignant

gliomas. Int J Pharm, 2012. 436(1-2): p. 299-310.

[9]Gao, M., Y. Chen, and C. Wu, Size-dependent

chemosensitization of doxorubicin-loaded polymeric

nanoparticles for malignant glioma chemotherapy.

Bioengineered, 2021. 12(2): p. 12263-12273.

[10]Liu, J., et al., Enhanced anti-tumor activity of a drug

through pH-triggered release and dual targeting by calcium

phosphate-covered mesoporous silica vehicles. J Mater Chem

B, 2022. 10(3): p. 384-395.

[11]Sun, Z., et al., Application of dual targeting drug

delivery system for the improvement of anti-glioma efficacy

of doxorubicin. Oncotarget, 2017. 8(35): p. 58823-58834.

[12]Matsumura, Y., Preclinical and clinical studies of

NK012, an SN-38-incorporating polymeric micelles, which

is designed based on EPR effect. Adv Drug Deliv Rev, 2011.

63(3): p. 184-92.

[13]Maeda, H., G.Y. Bharate, and J. Daruwalla,

Polymeric drugs for efficient tumor-targeted drug delivery

based on EPR-effect. Eur J Pharm Biopharm, 2009. 71(3): p.

409-19.

[14]Hamaguchi, T., et al., NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend

in vivo antitumour activity and reduce the neurotoxicity of

paclitaxel. Br J Cancer, 2005. 92(7): p. 1240-6.

[15]Villa, F., R. Quarto, and R. Tasso, Extracellular

Vesicles as Natural, Safe and Efficient Drug Delivery Systems.

Pharmaceutics, 2019. 11(11).

[16]Fenart, L., et al., Evaluation of effect of charge and

lipid coating on ability of 60-nm nanoparticles to cross an

in vitro model of the blood-brain barrier. J Pharmacol Exp

Ther, 1999. 291(3): p. 1017-22.

[17]Schinkel, A.H., et al., P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and

pharmacological activity of many drugs. J Clin Invest, 1996.

97(11): p. 2517-24.

[18]Lockman, P.R., et al., Nanoparticle technology for

drug delivery across the blood-brain barrier. Drug Dev Ind

Pharm, 2002. 28(1): p. 1-13.

[19]Rawat, P.S., et al., Doxorubicin-induced

cardiotoxicity: An update on the molecular mechanism and

novel therapeutic strategies for effective management. Biomed

Pharmacother, 2021. 139: p. 111708.

[20]Wenningmann, N., et al., Insights into

Doxorubicin-induced Cardiotoxicity: Molecular Mechanisms,

Preventive Strategies, and Early Monitoring. Molecular

Pharmacology, 2019. 96(2): p. 219-232.

[21]Batist, G., et al., Overexpression of a novel anionic

glutathione transferase in multidrug-resistant human breast

cancer cells. J Biol Chem, 1986. 261(33): p. 15544-9.


Refbacks

  • 当前没有refback。