Biodistribution, Safety and Organ Toxicity of Docetaxel-Loaded in HER-2 Aptamer Conjugated Ecoflex® Nanoparticles in a Mouse Xenograft Model of Ovarian Cancer

(E-pub Ahead of Print)

Author(s): Erfaneh Ghassami, Jaleh Varshosaz*, Mohsen Minaiyan, Mehrab Nasirikenari, Seyed Mohammad Hoseini.

Journal Name: Recent Patents on Nanotechnology

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Background: Docetaxel is a notably efficient anticancer drug administered for several types of malignancies including ovarian cancer. However, various side effects caused either by the nonspecific distribution of the active ingredient or by high contents of Tween 80 and ethanol in the currently marketed formulations, could even deprive the patients of the treatment. Objectives: In the current study, a novel targeted delivery system composed of Ecoflex® polymeric nanoparticles loaded with docetaxel and equipped with HER-2 specific aptamer molecules was evaluated regarding blood and tissue toxicity, and biodistribution. Methods: The tumor-bearing nude mice, achieved by subcutaneous injection of SKOV-3 cells, were divided into four groups treated with normal saline, Taxotere®, targeted docetaxel nanoparticles, and non-targeted docetaxel nanoparticles. Results: According to the results of hematologic evaluations, almost all hematologic parameters were in normal range with no significant difference among the four groups. Histopathological studies revealed that treatment with targeted nanoparticles caused a remarkable reduction in mitosis in tumor sections and overall reduced organ toxicity compared with Taxotere®. The only exception was spleen in which more damage was caused by the nanoparticles. The results of the biodistribution study were also in accordance with pathological assessments, with significantly lower drug concentration in non-tumor tissues, except for spleen, when targeted nanoparticles were used compared with Taxotere®. Conclusion: These results could evidence the efficiency of the targeted delivery system in concentrating the drug cargo mostly in its site of action leading to the elimination of its adverse effects caused by exposure of other tissues to the cytotoxic agent.

Keywords: Aptamer, biodistribution, docetaxel, ecoflex, nanoparticles, organ toxicity.

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(E-pub Ahead of Print)
DOI: 10.2174/1872210513666181128162403
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