Title: Targeted delivery of doxorubicin-loaded cockle shell-derived CaCO₃ aragonite nanoparticles on dogs with solid tumours

Authors: Abubakar Danmaigoro; Gayathri Thevi Selvarajah; Mohd Hezmee Mohd Noor; Rozi Mahmud; Hamidu Ahmed; Md Zuki Abubakar

Addresses: Faculty of Veterinary Medicine, Department of Veterinary Preclinical Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Faculty of Veterinary Medicine, Department of Veterinary Anatomy, Usmanu Danfodiyo University, P.M.B 2346, Sokoto, Nigeria ' Faculty of Veterinary Medicine, Department of Veterinary Clinical Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia ' Faculty of Veterinary Medicine, Department of Veterinary Preclinical Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia ' Faculty of Medicine and Health Science, Department of Imaging, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia ' Laboratory of Molecular Biomedicine, Institute of Biosains, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia ' Faculty of Veterinary Medicine, Department of Veterinary Preclinical Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

Abstract: The treatment of solid tumour remains a major challenge to oncologists. Even when chemotherapy is referred as the best treatment option thus associated with off targeted effect, with doxorubicin widely used but it application is impaired in its high concentration levels resulting in tissue injury, specifically, cardiotoxicity. However, advances in nanomedicine have paved the way for the search for an inorganic biomaterial with the potential to deliver doxorubicin (DOX) safely. Cockle shell-derived calcium carbonate (CaCO₃) nanoparticle-loaded with DOX has shown a promising potential in the pre-clinical studies. Thus, this trial is aimed at exploring the effectiveness of DOX-loaded cockle shell-derived calcium carbonate aragonite nanoparticles (CS-CaCO₃NP-DOX) on dogs with spontaneous tumours with aim of improving the overall survival rate and quality of life. A prospective single centre, non-blind open clinical trial of repeated doses of CS-CaCO₃NP-DOX on dogs with solid tumours was performed. The primary and secondary endpoints were evaluated every three weeks for 15 weeks. There was no major adverse effect observed within the period on the vital parameters, haematological and biochemical profile associated with the formulation. Although, partial response and progressive cRECIST response were recorded in the two cases enrolled within the study period, however, production of osteoid matrix, inhibition of cell proliferation and induction of osteogenic cell death were observed 48 h after treatment. This preliminary finding shows that biogenic CS-CaCO₃NP-DOX is potentially effective for treating bone cancer in dogs and improves the quality of life of dogs with solid tumours and further reveals the safety and anticancer efficiency of CS-CaCO₃NP-DOX in dogs with solid tumours.

Keywords: CS-CaCO₃NP; doxorubicin; clinical trial; dog; tumour.

DOI: 10.1504/IJNT.2019.107365

International Journal of Nanotechnology, 2019 Vol.16 No.11/12, pp.730 - 749

Published online: 18 May 2020 *

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