Abstract 2154: Bone metastasis targeting: a novel approach to reach bone using zoledronate anchored nanoparticles loaded with docetaxel.

Bone metastasis targeting remains largely unexplored. Some of the bone diseases are seldom cured just because of poor distribution of drug to the bone. Zoledronic acid (ZOL) possess a strong affinity towards bone, and hence its utility in bone metastasis management makes it a perfect ligand for bone targeting. Recent studies revealed that ZOL in combination with docetaxel (DTX) showed significant synergism in the management of bone metastasis. DTX-loaded ZOL-conjugated polyethylene glycol (PEG)ylated polybutyl cyanoacrylate (PBCA) NPs (PBCA-PEG-ZOL) were prepared using the anionic polymerization technique. Physiochemical Characterization, pharmacokinetics, in vitro bone binding assay, quantitative cellular uptake, NP uptake route characterization, and cellular IPP/ApppI (isopentenyl pyrophosphate/triphosphoric acid 1-adenosin-5′-yl ester 3-(3-methylbut-3-enyl) ester) levels were performed. DTX was efficiently entrapped (75.94 ± 3.82%) in the Zol conjugated NPs, estimated by HPLC. They had discrete spherical shape, and size of around 82 nm estimated by zetasizer and transmission electron microscopy. Biodistribution studies using technetium-99m radiolabeling showed prolonged blood circulation half-life, and that the ratio of PBCA-PEG-ZOL NPs in tumor bearing bone to the normal bone was 3 fold, at any time point. Further, ZOL conjugated NPs localization in tumor bearing bone significantly increased with time and found to be 7.5 (p Citation Format: Vinoth Kumar Megraj Khandelwal, Kiran R. Chaudhari, Abhinesh Kumar, Anil K. Mishra, Jukka Monkkonen, Rayasa S. Ramachandra Murthy. Bone metastasis targeting: a novel approach to reach bone using zoledronate anchored nanoparticles loaded with docetaxel. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2154. doi:10.1158/1538-7445.AM2013-2154