Chain length impact on the retro Diels-Alder mediated release of gemcitabine from hybrid nanoparticles towards pancreatic cancer therapy.

Oluwasanmi, Adeolu; Lindsay, Sarah; Curtis, Anthony; Perrie, Yvonne; Hoskins, Clare

Abstract

Previously reported gold coated iron oxide nanoparticles (Au-IONP's) have demonstrated their effectiveness as drug delivery vehicles for gemcitabine conjugated to a thermally labile Diels-Alder linker containing a chain of 4 carbon atoms (TTLD4) for the treatment of pancreatic cancer. Heat generated via laser irradiation of Au-IONPs facilitated retro Diels-Alder mediated release in a burst release profile where approximately half of all total release over 180 min occurred within the first 5 min. Two analogues of TTLD4, which differ only in linker chain length (TTLD3 & TTLD6) were synthesised and conjugated to Au-IONP's. Heat-mediated release of gemcitabine at 45 °C over 180 min from these formulations was confirmed to be based on linker length, which was 94%, 76% and 45% for TTLD3, TTLD4 and TTLD6, respectively. Drug loading of the Diels-Alder linkers in a 5:1 Drug/Au-IONP w/w ratio appears to favour those containing an even number of carbons TTLD4 (76%) & TTLD6 (57%) over TTLD3 (25%), possibly due to the linker likely being positioned perpendicular to the Au-IONP surface because of the 120 °C-C bond. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.]

Citation

Oluwasanmi, A., Lindsay, S., Curtis, A., Perrie, Y., & Hoskins, C. (2023). Chain length impact on the retro Diels-Alder mediated release of gemcitabine from hybrid nanoparticles towards pancreatic cancer therapy. International Journal of Pharmaceutics, 644, Article 123304. https://doi.org/10.1016/j.ijpharm.2023.123304

• Journal Article Type: Article
• Acceptance Date: Aug 9, 2023
• Online Publication Date: Aug 10, 2023
• Publication Date: Sep 25, 2023
• Deposit Date: Sep 7, 2023
• Journal: International journal of pharmaceutics
• Print ISSN: 0378-5173
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 644
• Article Number: 123304
• DOI: https://doi.org/10.1016/j.ijpharm.2023.123304
• Keywords: Gemcitabine, Retro Diels-Alder, Pancreatic cancer, Hybrid nanoparticle, Thermo responsive drug delivery