Oluwasanmi, A and Al-Shakarchi, W and Manzur, A and Aldebasi, MH and Elsini, RS and Albusair, MK and Haxton, KJ and Curtis, ADM and Hoskins, C (2017) Diels Alder-mediated release of gemcitabine from hybrid nanoparticles for enhanced pancreatic cancer therapy. Journal of Controlled Release. ISSN 0168-3659

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Abstract

Abstract Hybrid nanoparticles (HNPs) have shown huge potential as drug delivery vehicles for pancreatic cancer. Currently, the first line treatment, gemcitabine, is only effective in 23.8% of patients. To improve this, a thermally activated system was developed by introducing a linker between HNPs and gemcitabine. Whereby, heat generation resulting from laser irradiation of the HNPs promoted linker breakdown resulting in prodrug liberation. In vitro evaluation in pancreatic adenocarcinoma cells, showed the prodrug was 4.3 times less cytotoxic than gemcitabine, but exhibited 11-fold improvement in cellular uptake. Heat activation of the formulation led to a 56% rise in cytotoxicity causing it to outperform gemcitabine by 26%. In vivo the formulation outperformed free gemcitabine with a 62% reduction in tumor weight in pancreatic xenografts. This HNP formulation is the first of its kind and has displayed superior anti-cancer activity as compared to the current first line drug gemcitabine after heat mediated controlled release.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier at http://dx.doi.org/10.1016/j.jconrel.2017.09.027 - please refer to any applicable terms of of the publisher.
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy
Depositing User: Symplectic
Date Deposited: 22 Sep 2017 10:44
Last Modified: 25 Sep 2017 10:10
URI: http://eprints.keele.ac.uk/id/eprint/4045

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