Doxorubicin-intercalated nano-hydroxyapatite drug-delivery system for liver cancer: An animal model

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, and satisfactory treatment is unavailable. Doxorubicin (DOX) is commonly used for HCC treatment with very limited success and serious side-effects such as cardiotoxicity and non-cancer cell cytotoxicity. In...

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Bibliographic Details
Published in:Ceramics international 2013-12, Vol.39 (8), p.9557-9566
Main Authors: Kundu, Biswanath, Ghosh, Debasree, Sinha, Mithlesh Kumar, Sen, Partha Sarathi, Balla, Vamsi Krishna, Das, Nirmalendu, Basu, Debabrata
Format: Article
Language:English
Subjects:
Animals
Doxorubicin
HAp-DOX conjugate
Hepatocellular carcinoma
In vivo
Liver
Morphology
Nano-hydroxyapatite
Nanocomposites
Nanomaterials
Nanoparticles
Nanostructure
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Summary:Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, and satisfactory treatment is unavailable. Doxorubicin (DOX) is commonly used for HCC treatment with very limited success and serious side-effects such as cardiotoxicity and non-cancer cell cytotoxicity. In the present investigation, a new nano-sized hydroxyapatite (HAp)-based drug-delivery system was successfully developed with nano-sized hydroxyapatite (HAp) (sizes 5–30nm) and synthesised with a Ca/P molar ratio of 1.67. After thorough in vitro characterisation, these nano-HAP particles were loaded/intercalated with DOX (50–60% encapsulation efficiency), and thorough characterisation of the size, shape and morphology of the particles was performed. The average drug-loaded nanoparticles had a spherical morphology with a size range of 40–60nm. The in vitro drug-elution kinetics were examined under different pH conditions to account for the actual pH conditions found in the body environment. The kinetics were observed to be ideal for IV therapy to treat HCC. In vivo experiments using animal models demonstrated very promising results in terms of relative liver weight changes and histopathology. Ultimately, ‘high-dose’ HAp-DOX produced maximum suppression of hyperplastic nodules and a minimum number of preneoplastic lesions. In summary, our results indicate that this new formulation is an efficient, safe and reliable treatment method for HCC.
ISSN:0272-8842
1873-3956
DOI:10.1016/j.ceramint.2013.05.074