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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Construction of Gambogic Acid HPMA Copolymer Coupling Drug System and Study on Anti-tumor Activity

Author(s): Xinghua Zhao, Shi Ding, Shengnan Li, Yang Wang, Mingjun Jiang, Ju Liu* and Ye Chen*

Volume 19, Issue 4, 2022

Published on: 10 January, 2022

Page: [491 - 507] Pages: 17

DOI: 10.2174/1567201818666210729102921

Price: $65

Abstract

Aim: An active-passive dual-targeting gambogic acid HPMA Copolymer Coupling drug system with high efficiency, low toxicity and high selectivity was constructed.

Methods: The gambogic acid HPMA copolymer coupling drug system was constructed and its structure was characterized. The cytotoxicity of gambogic acid HPMA copolymer was detected by MTT assay. The pharmacokinetics of gambogic acid HPMA copolymer was evaluated in mice. Targetability of gambogic acid HPMA copolymer was evaluated by tissue distribution experiment. The in vitro antitumor activity of gambogic acid HPMA copolymer was evaluated by pharmacodynamics experiment in mice.

Results: Two copolymers of gambogic acid HPMA were successfully prepared. The copolymers showed reduced cytotoxicity and a certain sustained release effect and targeting property. In vivo pharmacodynamic experiments also showed better anti-tumor effects than GA.

Discussion: In this study, gambogic acid was combined with HPMA polymer and the targeting molecule D-galactose/folic acid to form a polymer micelle with high efficiency, low toxicity and high selectivity for active-passive dual targeting. The construction of the drug system provides new ideas for future formulation research and development.

Keywords: Gambogic acid, HPMA polymer, D-galacto, folic acid, synthesis, targeted drug.

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[1]
Chen, W.Q.; Li, H.; Sun, K.X.; Zheng, R.S.; Zhang, S.W.; Zeng, H.M.; Zou, X.N.; Gu, X.Y.; He, J. Report of cancer incidence and mortality in china, 2014. Zhonghua Zhong Liu Za Zhi, 2018, 40(1), 5-13.
[http://dx.doi.org/10.3760/cma.j.issn.0253-3766.2018.01.002] [PMID: 29365411]
[2]
Zhang, Z.J. Synthesis and antitumor activities of novel Aryl-substituted gambogic acid derivatives. Guangzhou Medical University, 2015.
[http://dx.doi.org/10.7666/d.D714790]
[3]
Subramanian, V.; Ducept, P.; Williams, R.M. Effects of photochemically activated alkylating agents of the FR900482 family on chromatin. Chem. Biol., 2007, 14(5), 553-563.
[http://dx.doi.org/10.1016/j.chembiol.2007.04.004] [PMID: 17524986]
[4]
Wu, P.; Xu, H.Q.; Zhao, J.F. Knockdown of BLM Helicase promotes the sensitivity of prostate cancer PC3 cells to mitomycin C. Chinese J. Biochem. Mol. Biol., 2017, 33(2), 190-197.
[http://dx.doi.org/10.13865/j.cnki.cjbmb.2017.02.13]
[5]
Qian, Y.; Zhang, R.; Jing, W.U. Advances in antitumor mechanism of oncolytic virus and its clínical application. Tumor, 2018, 38(5), 513-518.
[http://dx.doi.org/10.3781/j.issn.1000-7431.2018.55.494]
[6]
Xin, J.L.; Fan, Q. Application of noval drug delivery system on reversal of tumor multidrug resistance. Practical Pharmacy And Clinical Remedies, 2010. (4).
[http://dx.doi.org/10.3969/j.issn.1673-0070.2010.04.019]
[7]
Wang, Q.; Cui, P.P.; Yuan, J.F. Preparation of micelles from an amphiphilic block copolymer and their loading and controlled release of folic acid. Acta Polymerica Sinica, 2011, (12), 1361-1367.
[http://dx.doi.org/10.3724/SP.J.1105.2011.10300]
[8]
Zhang, W.P.; Chen, Y.W.; Zhang, K. Research of folic acid mediated targeted drug delivery system. Chinese Arch. Trad. Chinese Med., 2017, 35(7), 1855-1859.
[http://dx.doi.org/10.13193/j.issn.1673-7717.2017.07.060]
[9]
Huang, W.; Wang, X.; Shi, C.; Guo, D.; Xu, G.; Wang, L.; Bodman, A.; Luo, J. Fine-tuning vitamin E-containing telodendrimers for efficient delivery of gambogic acid in colon cancer treatment. Mol. Pharm., 2015, 12(4), 1216-1229.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00051] [PMID: 25692376]
[10]
Xiang, L.; Chunhui, Z.; Jie, X. Nanoparticles as drug delivery system in diagnosis and therapy of solid brain tumor. Zhongguo Zhongliu Shengwu Zhiliao Zazhi, 2015, 22(2), 265-271.
[http://dx.doi.org/10.3872/j.issn.1007-385X.2015.02.023]
[11]
Jian, Y.J.; Wang, X.S.; Huang, P. Preparation and quality control of neogambogic acid hydroxypropyl-β-cyclodextrin inclusion complex. Zhongguo Xin Yao Zazhi, 2010, 19(7), 628-631.
[12]
Chen, J.; Cheng, Y.; Zheng, P.J. Optimization of enzymatic synthesis of asialoglycoprotein receptor ligand cholesterol-vinyl sebacate-lactitol. Chin. Tradit. Herbal Drugs, 2015, 46(4), 502-506.
[13]
Zhang, Y.J.; Li-Hua, H.U.; Chen, P. Expression of folate receptor alpha in the tissues and cells of primary carcinoma of the liver.China Practical Med; , 2013, 8, p. (10)8-9.
[http://dx.doi.org/10.3969/j.issn.1673-7555.2013.10.004]
[14]
Mishra, G.; Hazari, P.P.; Kumar, N.; Mishra, A.K. In vitro and in vivo evaluation of 99mTc-DO3A-EA-Folate for receptor-mediated targeting of folate positive tumors. J. Drug Target., 2011, 19(9), 761-769.
[http://dx.doi.org/10.3109/1061186X.2011.561857] [PMID: 21425922]
[15]
Chen, H.L.; Liu, X.J.; Zhai, G.X. Advances in research on folate receptor-mediated targeted delivery systems. Hebei J. Industrial Sci.Technol., 2020, 37(2), 120-127.
[http://dx.doi.org/10.7535/hbgykj.2020yx02011]

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