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. Methods: In the present investigation, a new nano-sized hydroxyapatite (HAp)-based drug-delivery system was successfully developed with nano-sized hydroxyapatite (HAp) (sizes 5-30 nm) 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. Results: The average drug-loaded nanoparticles had a spherical morphology with a size range of 40-60 am. 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. 2013 Elsevier Ltd and Techna Group S.r.l. All rights reserved.