Chitosan stabilized camptothecin nanoemulsions: Development, evaluation and biodistribution in preclinical breast cancer animal mode

作者: Subramanian Natesan , Abimanyu Sugumaran , Chandrasekar Ponnusamy , Vignesh Thiagarajan , Rajaguru Palanichamy

DOI: 10.1016/J.IJBIOMAC.2017.05.127

关键词:

摘要: Clinical use of camptothecin (CPT) is hindered due to its poor water and oil solubility, active lactone ring instability non-targeted toxicity. Recently we reported formulation microemulsions with increased solubility for the improved treatment breast cancer. In this research chitosan stabilized nanoemulsions (CHI-CPT-NEs) were formulated improve cancer targeting efficiency CPT. The developed NEs characterized their droplet size distribution, stability in plasma evaluated in-vitro drug release, in-vivo potential, hemolytic cytotoxicity, genotoxicity biodistribution. CHI-CPT-NEs showed uniform extended release (61.65±1.57% at 24h), tolerable potential (16.4±1.4%), significant cytotoxicity (178±4.3ng/ml) against MCF-7 cells low DNA damage lymphocytes. In-vivo biodistribution study conducted 4T1-breast tumor xenograft BALB/c mice that 2495.22±174.66ng/gm was passively targeted by compared non-stabilized nanoemulsion (1677.58±134.21ng/gm). Thus, passive may provide a promising approach efficient therapy.

参考文章(29)
Y H Hsiang, R Hertzberg, S Hecht, L F Liu, Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. Journal of Biological Chemistry. ,vol. 260, pp. 14873- 14878 ,(1985) , 10.1016/S0021-9258(17)38654-4
A. Hatefi, B. Amsden, Camptothecin delivery methods. Pharmaceutical Research. ,vol. 19, pp. 1389- 1399 ,(2002) , 10.1023/A:1020427227285
Chan-Juan Hu, Xiu-Li Zhao, Ji-zhong Li, Shuang-Ming Kang, Chun-Rong Yang, Yun-Huan Jin, Dan Liu, Da-Wei Chen, Preparation and characterization of β-elemene-loaded microemulsion. Drug Development and Industrial Pharmacy. ,vol. 37, pp. 765- 774 ,(2011) , 10.3109/03639045.2010.541261
Ae-Jin Choi, Chul-Jin Kim, Yong-Jin Cho, Jae-Kwan Hwang, Chong-Tai Kim, Characterization of Capsaicin-Loaded Nanoemulsions Stabilized with Alginate and Chitosan by Self-assembly Food and Bioprocess Technology. ,vol. 4, pp. 1119- 1126 ,(2011) , 10.1007/S11947-011-0568-9
Chris H. Takimoto, John Wright, Susan G. Arbuck, Clinical applications of the camptothecins Biochimica et Biophysica Acta. ,vol. 1400, pp. 107- 119 ,(1998) , 10.1016/S0167-4781(98)00130-4
Thiruganesh Ramasamy, Tuan Hiep Tran, Hyuk Jun Cho, Jeong Hwan Kim, Yong Il Kim, Jae Yoon Jeon, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim, Chitosan-Based Polyelectrolyte Complexes as Potential Nanoparticulate Carriers: Physicochemical and Biological Characterization Pharmaceutical Research. ,vol. 31, pp. 1302- 1314 ,(2014) , 10.1007/S11095-013-1251-9
Yan Gao, Ling Bing Li, Guangxi Zhai, Preparation and characterization of Pluronic/TPGS mixed micelles for solubilization of camptothecin. Colloids and Surfaces B: Biointerfaces. ,vol. 64, pp. 194- 199 ,(2008) , 10.1016/J.COLSURFB.2008.01.021
Subramanian Natesan, Abimanyu Sugumaran, Chandrasekar Ponnusamy, Vinoth Jeevanesan, Gangarani Girija, Rajaguru Palanichamy, Development and evaluation of magnetic microemulsion: tool for targeted delivery of camptothecin to BALB/c mice-bearing breast cancer. Journal of Drug Targeting. ,vol. 22, pp. 913- 926 ,(2014) , 10.3109/1061186X.2014.948878
Peggy L Olive, Judit P Banáth, The comet assay: a method to measure DNA damage in individual cells. Nature Protocols. ,vol. 1, pp. 23- 29 ,(2006) , 10.1038/NPROT.2006.5