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

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Oluwasanmi, Adeolu and Lindsay, Sarah and Curtis, Anthony and Perrie, Yvonne and Hoskins, Clare (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. 123304. ISSN 1873-3476 (https://doi.org/10.1016/j.ijpharm.2023.123304)

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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.

ORCID iDs

Oluwasanmi, Adeolu, Lindsay, Sarah, Curtis, Anthony, Perrie, Yvonne and Hoskins, Clare ORCID logoORCID: https://orcid.org/0000-0002-7200-0566;
CORE (COnnecting REpositories)