ArticleOncotarget2017
Nanocrystals of a new camptothecin derivative WCN-21 enhance its solubility and efficacy.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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9 authors.
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Abstract
WCN-21 is a new camptothecin derivative we synthesized and has desirable anti-tumor efficacy, but its aqueous solubility is very low and hurdles the further evaluation and development. In this study, we prepared nanocrystals of WCN-21 through a bottom-up approach to enhance its solubility and obtained WCN-21 nanorods (WND) and nanospheres (WNP). We investigated the crystallization of WND and WNP in different temperature and solvents and found that both temperature and solvents affect the crystal shapes and sizes. We prepared WND at 50°C and DMSO : H2O 1: 50 and WNP at 25°C and DMSO : H2O 1: 100 and found they were dispersed evenly in water with average hydrodynamic diameters 337 and 231 nm, respectively. WND and WNP increased the solubility of WCN-21 from extreme insolubility to more than 9 and 11 mM in H2O or PBS, respectively. In vitro studies showed that WND and WNP enhanced the uptake of WCN-21 in tumor cells by 3 and 9 folds, and increased cytotoxicity of WCN-21 in comparison with free WCN-21 by 5 and 6 folds, respectively. In xenograft tumor mice, intravenous injection of WND and WNP enhanced the accumulation of WCN-21 in tumor tissues and improved the anti-tumor efficacy. In addition, WND and WNP did not increase the toxicity of WCN-21 in mice. Therefore, nanocrystal is a robust tool to improve the solubility of insoluble drugs and holds a great potential in the application of drug development.
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