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Toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs

Doxorubicin (DOX) is a potent anticancer agent with cytotoxic effects which limit its clinical usage. This effect is due to its nonselective nature causing injury to the cells as a result of reactive free oxygen radical's release. Cockleshell-derived calcium carbonate nanoparticle (CS-CaCO3NP)...

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Main Authors: Danmaigoro, Abu Bakar, Selvarajah, Gayathri Thevi, Mohd Noor, Mohd Hezmee, Mahmud, Rozi, Abu Bakar @ Zakaria, Md Zuki
Format: Article
Language:English
Published: Hindawi 2018
Online Access:http://psasir.upm.edu.my/id/eprint/74325/1/Toxicity%20and%20safety%20evaluation%20of%20doxorubicin-loaded%20cockleshell-derived%20calcium%20carbonate%20nanoparticle%20in%20dogs.pdf
http://psasir.upm.edu.my/id/eprint/74325/
https://www.hindawi.com/journals/aps/2018/4848602/
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spelling my.upm.eprints.743252020-04-22T17:25:27Z http://psasir.upm.edu.my/id/eprint/74325/ Toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs Danmaigoro, Abu Bakar Selvarajah, Gayathri Thevi Mohd Noor, Mohd Hezmee Mahmud, Rozi Abu Bakar @ Zakaria, Md Zuki Doxorubicin (DOX) is a potent anticancer agent with cytotoxic effects which limit its clinical usage. This effect is due to its nonselective nature causing injury to the cells as a result of reactive free oxygen radical's release. Cockleshell-derived calcium carbonate nanoparticle (CS-CaCO3NP) is a pH-responsive carrier with targeted delivery potentials. This study aimed at evaluating the toxicity effects of repeated dose administration of DOX-loaded CS-CaCO3NP in healthy dogs. Fifteen dogs with an average body weight of 15 kg were randomized equally into 5 groups. Dogs were subjected to 5 doses at every 3-week interval with (i) normal saline, (ii) DOX, 30 mg/m2, and the experimental groups: CS-CaCO3NP-DOX at (iii) high dose, 50 mg/m2, (iv) clinical dose, 30 mg/m2, and (v) low dose, 20 mg/m2. Radiographs, electrocardiography, and blood samples were collected before every treatment for haematology, serum biochemistry, and cardiac injury assessment. Heart and kidney tissues were harvested after euthanasia for histological and ultrastructural evaluation. The cumulative dose of DOX 150 mg/m2 over 15 weeks revealed significant effects on body weight, blood cells, functional enzymes, and cardiac injury biomarkers with alterations in electrocardiogram, myocardium, and renal tissue morphology. However, the dogs given CS-CaCO3NP-DOX 150 mg/m2 and below did not show any significant change in toxicity biomarker as compared to those given normal saline. The study confirmed the safety of repeated dose administration of CS-CaCO3NP-DOX (30 mg/m2) for 5 cycles in dogs. This finding offers opportunity to dogs with cancer that might require long-term administration of DOX without adverse effects. Hindawi 2018 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/74325/1/Toxicity%20and%20safety%20evaluation%20of%20doxorubicin-loaded%20cockleshell-derived%20calcium%20carbonate%20nanoparticle%20in%20dogs.pdf Danmaigoro, Abu Bakar and Selvarajah, Gayathri Thevi and Mohd Noor, Mohd Hezmee and Mahmud, Rozi and Abu Bakar @ Zakaria, Md Zuki (2018) Toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs. Advances in Pharmacological Sciences, 2018. art. no. 4848602. pp. 1-20. ISSN 1687-6334; ESSN: 1687-6342 https://www.hindawi.com/journals/aps/2018/4848602/
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Doxorubicin (DOX) is a potent anticancer agent with cytotoxic effects which limit its clinical usage. This effect is due to its nonselective nature causing injury to the cells as a result of reactive free oxygen radical's release. Cockleshell-derived calcium carbonate nanoparticle (CS-CaCO3NP) is a pH-responsive carrier with targeted delivery potentials. This study aimed at evaluating the toxicity effects of repeated dose administration of DOX-loaded CS-CaCO3NP in healthy dogs. Fifteen dogs with an average body weight of 15 kg were randomized equally into 5 groups. Dogs were subjected to 5 doses at every 3-week interval with (i) normal saline, (ii) DOX, 30 mg/m2, and the experimental groups: CS-CaCO3NP-DOX at (iii) high dose, 50 mg/m2, (iv) clinical dose, 30 mg/m2, and (v) low dose, 20 mg/m2. Radiographs, electrocardiography, and blood samples were collected before every treatment for haematology, serum biochemistry, and cardiac injury assessment. Heart and kidney tissues were harvested after euthanasia for histological and ultrastructural evaluation. The cumulative dose of DOX 150 mg/m2 over 15 weeks revealed significant effects on body weight, blood cells, functional enzymes, and cardiac injury biomarkers with alterations in electrocardiogram, myocardium, and renal tissue morphology. However, the dogs given CS-CaCO3NP-DOX 150 mg/m2 and below did not show any significant change in toxicity biomarker as compared to those given normal saline. The study confirmed the safety of repeated dose administration of CS-CaCO3NP-DOX (30 mg/m2) for 5 cycles in dogs. This finding offers opportunity to dogs with cancer that might require long-term administration of DOX without adverse effects.
format Article
author Danmaigoro, Abu Bakar
Selvarajah, Gayathri Thevi
Mohd Noor, Mohd Hezmee
Mahmud, Rozi
Abu Bakar @ Zakaria, Md Zuki
spellingShingle Danmaigoro, Abu Bakar
Selvarajah, Gayathri Thevi
Mohd Noor, Mohd Hezmee
Mahmud, Rozi
Abu Bakar @ Zakaria, Md Zuki
Toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs
author_facet Danmaigoro, Abu Bakar
Selvarajah, Gayathri Thevi
Mohd Noor, Mohd Hezmee
Mahmud, Rozi
Abu Bakar @ Zakaria, Md Zuki
author_sort Danmaigoro, Abu Bakar
title Toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs
title_short Toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs
title_full Toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs
title_fullStr Toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs
title_full_unstemmed Toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs
title_sort toxicity and safety evaluation of doxorubicin-loaded cockleshell-derived calcium carbonate nanoparticle in dogs
publisher Hindawi
publishDate 2018
url http://psasir.upm.edu.my/id/eprint/74325/1/Toxicity%20and%20safety%20evaluation%20of%20doxorubicin-loaded%20cockleshell-derived%20calcium%20carbonate%20nanoparticle%20in%20dogs.pdf
http://psasir.upm.edu.my/id/eprint/74325/
https://www.hindawi.com/journals/aps/2018/4848602/
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score 13.211869

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