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Cyclodextrin diethyldithiocarbamate copper ii inclusion complexes: A promising chemotherapeutic delivery system against chemoresistant triple negative breast cancer cell lines
Suliman, AS Khoder, M Tolaymat, I Webster, M Alany, RG Wang, W Elhissi, A Najlah, M
Suliman, AS
Khoder, M
Tolaymat, I
Webster, M
Alany, RG
Wang, W
Elhissi, A
Najlah, M
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2021-01-10
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Abstract
Diethyldithiocarbamate Copper II (DDC-Cu) has shown potent anticancer activity against a wide range of cancer cells, but further investigations are hindered by its practical insolubility in water. In this study, inclusion complexes of DDC-Cu with hydroxypropyl beta-cyclodextrin (HP) or sulfobutyl ether beta-cyclodextrin (SBE) were prepared and investigated as an approach to enhance the apparent solubility of DDC-Cu. Formulations were prepared by simple mixing of DDC-Cu with both cyclodextrin (CDs) at room temperature. Phase solubility assessments of the resulting solutions were performed. DDC-Cu CD solutions were freeze-dried for further characterisations by DSC, thermogravimetric analysis (TGA) and FT-IR. Stability and cytotoxicity studies were also performed to investigate the maintenance of DDC-Cu anticancer activity. The phase solubility profile deviated positively from the linearity (Ap type) showing significant solubility enhancement of the DDC-Cu in both CD solutions (approximately 4 mg/mL at 20% w/w CD solutions). The DSC and TGA analysis confirmed the solid solution status of DDC-Cu in CD. The resulting solutions of DDC-Cu were stable for 28 days and conveyed the anticancer activity of DDC-Cu on chemoresistant triple negative breast cancer cell lines, with IC50 values less than 200 nM. Overall, cyclodextrin DDC-Cu complexes offer a great potential for anticancer applications, as evidenced by their very positive effects against chemoresistant triple negative breast cancer cells.
Citation
Said Suliman A, Khoder M, Tolaymat I, Webster M, Alany RG, Wang W, Elhissi A, Najlah M. (2021) Cyclodextrin Diethyldithiocarbamate Copper II Inclusion Complexes: A Promising Chemotherapeutic Delivery System against Chemoresistant Triple Negative Breast Cancer Cell Lines. Pharmaceutics. 2021; 13(1):84. https://doi.org/10.3390/pharmaceutics13010084
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Research Unit
PubMed ID
33435151 (pubmed)
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Journal article
Language
en
Description
© 2021 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/pharmaceutics13010084
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1999-4923
EISSN
1999-4923
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This research is funded by NPRP grant (NPRP9-337-3-069) from the Qatar National Research Fund (a member of Qatar Foundation).
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Licence for published version: Creative Commons Attribution 4.0 International