Synthesis and in vitro Evaluation of Levothyroxine- Targeted Paclitaxel-Dextran Conjugate for Drug Delivery to Cancer Cells

Document Type : Original Article

Authors

1 Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

2 Research Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

10.30476/tips.2023.99454.1204

Abstract

Taxanes are a class of potent anticancer agents used in different cancers. Their low water solubility is the major challenge in formulation development that leads to the use of surfactants and organic solvents which causes severe hypersensitivity reactions. In this study, paclitaxel (PTX) was conjugated to a water-soluble and biocompatible polymer, dextran, to enhance solubility. Levothyroxine was also conjugated to dextran to provide targeted delivery. The cytotoxicity was studied on HepG2 and A375 cell lines before and after treating cell lines with levothyroxine. Results showed approximately 1250-fold water solubility enhancement by dextran conjugation. Drug conjugates presented higher cytotoxicity on A375 cell lines than its free drug counterparts at 10 and 50 nM concentrations after 24 hours. Pre-treatment with levothyroxine decreased the cytotoxicity on A375 as an integrin receptor rich cell line but did not show any significant effect on HepG2 cells which is low in expressing integrin receptor. In conclusion, preparation of levothyroxine targeted dextran conjugate might be an effective strategy for PTX delivery to different cell lines. 

Highlights

Fatemeh Ahmadi (Google Scholar)

Ali dehshahri (Google Scholar)

Elahehnaz Parhizkar (Google Scholar)

Keywords

References


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Trends in Pharmaceutical Sciences
Volume 9, Issue 3
September 2023
Pages 213-220

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