Cyclodextrin Diethyldithiocarbamate Copper II Inclusion Complexes: A Promising Chemotherapeutic Delivery System against Chemoresistant Triple Negative Breast Cancer Cell Lines

Said Suliman, Ammar, Khoder, Mouhamad, Tolaymat, Ibrahim, Webster, Matt, Alany, Raid G., Wang, Weiguang, Elhissi, Abdelbary M. A. and Najlah, Mohammad (2021) Cyclodextrin Diethyldithiocarbamate Copper II Inclusion Complexes: A Promising Chemotherapeutic Delivery System against Chemoresistant Triple Negative Breast Cancer Cell Lines. Pharmaceutics, 13 (1). p. 84. ISSN 1999-4923

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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.

Item Type:	Journal Article
Keywords:	diethyldithiocarbamate copper II, beta-cyclodextrin, chemoresistance, triple negative breast cancer, solubility
Faculty:	Faculty of Health, Education, Medicine & Social Care
SWORD Depositor:	Symplectic User
Depositing User:	Symplectic User
Date Deposited:	12 Jan 2021 16:31
Last Modified:	09 Sep 2021 18:51
URI:	https://arro.anglia.ac.uk/id/eprint/706170

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