A Copper10-Paclitaxel crystal; a medicinally active drug delivery platform

• Published in: Bioorganic & medicinal chemistry letters 2018-11, Vol.28 (20), p.3409-3417
• Main Authors: Manning, Thomas, Slaton, Christopher, Myers, Nia, Patel, Pavan D., Arrington, Domonique, Patel, Zalak, Phillips, Dennis, Wylie, Greg, Goddard, Russell
• Format: Article
• Language: English
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.08.019

Paclitaxel is a well-known cancer drug that functions as a mitotic inhibitor. This work focuses on a copper based crystal that encapsulates the pharmaceutical agent and serves as a drug delivery agent. A Copper10-Pacitaxil1 chloride (CU10PAC1) complex is synthesized and tested against the National Cancer Institute’s sixty cell line panel. The 10:1 ratio results in a crystal that was examined by Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF-MS), Scanning Electron Microscopy (SEM) and Proton (1H) and Carbon (13C) Nuclear Magnetic Resonance (NMR). The potential attributes of a copper based crystal as an in vivo drug carrier for Paclitaxel are discussed. [Display omitted] •A copper crystal is developed as a delivery vehicle for Paclitaxel.•The crystal slowly dissolves providing a novel time release approach to drug delivery.•Cancer patients have higher than normal copper, bound to proteins, levels in their serum.•Despite the slow release, in vitro tests indicate a similar level of efficacy as pure Paclitaxel.•The copper (I) chloride, a weak electrolyte, forms with strong crystal with Paclitaxel than a Cu(II) salt would. Paclitaxel is a well-known cancer drug that functions as a mitotic inhibitor. This work focuses on a copper based crystal that encapsulates the pharmaceutical agent and serves as a drug delivery agent. A Copper10-Pacitaxil1 chloride (CU10PAC1) complex is synthesized and tested against the National Cancer Institute’s sixty cell line panel. The 10:1 ratio results in a crystal that was examined by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spec (MALDI-TOF-MS), Scanning Electron Microscopy (SEM) and Proton (1H) and Carbon (13C) Nuclear Magnetic Resonance (NMR). The potential attributes of a copper based crystal as an in vivo drug carrier for Paclitaxel are discussed.