Fatemeh Movahedi, Wenyi Gu, Zhi Ping Xu *

 

Australian Institute for Bioengineering and Nanotechnology
The University of Queensland
Brisbane, Queensland, Australia
*Email: 
gordonxu@uq.edu.au

 

Initially recognised and widely used as an anti-parasitic drug for over 100 millions of populations, albendazole has recently emerged as an effective anticancer agent1,2. However, the application is limited due to its very poor water solubility3. Many strategies have been explored to improve albendazole solubility while formulating into nanoparticles is the most promising.

    Lipid-coated calcium phosphate (LCP) nanoparticle (NP) has properties such as biodegradability, biocompatibility and small size (less than 100 nm), which make LCP NP as a good choice for drug and gene delivery4. Further, LCPs are able to release their cargo depending on the acidity of the environment, such as the tumour environment5.

    In this work, we designed and loaded albendazole into LCP NPs to establish a drug delivery system for effective cancer treatment with less toxicity to normal cells. Albendazole-loaded LCP (ABZ-LCP) NPs were 50 nm in size and improved the solubility of albendazole form 10 μg/ml in free form to 25 μg/ml after 48 h in PBS. ABZ-LCP NPs demonstrated pH-responsiveness by releasing 77% and 29% of loaded albendazole in pH 5 and pH 7.4 solution after 72 h, respectively.

    In order to evaluate the anticancer activity of ABZ-LCP NPs, three cancerous cell lines, i.e. B16, MCF7 and HCT116 were treated with free albendazole, blank LCP and ABZ-LCP NPs for 4h (short term) and 72h (long term). No significant difference between free albendazole and ABZ-LCP NPs was observed for B16 cells, while treating MCF7 and HCT116 cells with ABZ-LCP NPs led to a considerable enhancement in both short term and long term treatment. Moreover, ABZ-LCP did not show any notable toxicity to healthy cell line HEK293T.

    To investigate the mechanism of cell growth suppression, apoptosis induction and VEGF expression were evaluated. The apoptosis rate of HCT116 cells treated with ABZ-LCP NPs and free albendazole was 55% and 43%, respectively, and the rate was 36% and 21% for MCF7 cells, demonstrating the significant apoptosis induction with LCP NPs. No evident difference in VEGF expression was observed for free albendazole and ABZ-LCP NPs.

    In conclusion, ABZ-LCP NPs are as a promising drug delivery system for cancer therapy. Such a system can enhance albendazole solubility and its toxicity against cancer cell lines while being safe to healthy cells. Further in vivo studies are necessary to confirm the anticancer efficacy of the system.

Reference

1 Noorani, L., Stenzel, M., Liang, R, Pourgholami, MH., Morris, DL. Journal of Nanobiotechnology 2015, 13, 25-37. Albumin nanoparticles increase the anticancer efficacy of albendazole in ovarian cancer xenograft model.

 2 Castro, LSEW., Kviecinski, MR., Ourique, F. Redox Biology 2016, 10, 90-99. Albendazole as a promising molecule for tumor control.

 3 Hettiarachchi, G., Samanta, SK., Falcinelli, S. Molecular Pharmaceutics 2016, 13, 809-818. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

 4 Xu, X., Li, Z., Zhao, X., Keen, L., Kong, X. Regenerative Biomaterial 2016, 3,187-195. Calcium phosphate nanoparticles-based systems for siRNA delivery.

  5 Tang, J., Li, L., Howard, CB., Mahler, SM., Huang, L., Xu, ZP. Journal of Material Chemistry B 2015, 3, 6805-6812. Preparation of optimized lipid-coated calcium phosphate nanoparticles for enhanced in vitro gene delivery to breast cancer cells.

Venue

Room: 
Hawken N201