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Synthesis of Pectin-Deoxycholic Acid Conjugate for Targeted Delivery of Anticancer Drugs in Hepatocellular Carcinoma Publisher Pubmed



Varshosaz J1 ; Sadri F1 ; Rostami M2 ; Mirian M3 ; Taymouri S1
Authors
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Authors Affiliations
  1. 1. Novel Drug Delivery Systems Research Center, Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Source: International Journal of Biological Macromolecules Published:2019


Abstract

Sorafenib (SF) a chemotherapeutic drug is used in hepatocellular carcinoma (HCC) with vast side effects. The aim of the project ahead was synthesis of SF loaded co-polymeric micelles of pectin-deoxycholic acid (P-DOCA) to target the overexpressed asialoglycoprotein receptors of hepatocytes by pectin. DOCA was modified with ethylenediamine and conjugated to pectin. FT-IR and 1HNMR confirmed the bio-conjugation. Pyrene was used to measure critical micelle concentration (CMC) by fluorimetry technique. P-DOCA micelles were loaded with SF and their particle size, zeta potential, drug loading and release efficiency were measured. MTT assay was used for determining cytotoxicity. The cell cycle arrest was studied by flow cytometry analysis and the cellular uptake was studied using cumarin-6 as the fluorophore agent. The micelles capability in preventing the cells migration was tested by Transwell plates. The CMC of P-DOCA micelles was 10.747 μg/mL. The best formulation obtained from SF to polymer ratio of 1:2. SF loaded micelles showed 30% increased cytotoxicity. The micelles cellular uptake was more than the free drug. Relative migration of HepG2 cells treated with SF loaded micelles was reduced to 6.67% compared to free SF which was 26.67%. The designed micelles are promising for antitumor drug targeting to HCC. © 2019
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