Synthesis of L-DOPA conjugated doxorubicin-polyethylenimine nanocarrier and evaluation of its cytotoxicity on A375 and HepG2 cell lines

Document Type : Research Paper


1 Pharmaceutical Sciences Research center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Pharmaceutics, 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


Objective(s): Polyethylenimine (PEI) is one of the most-extensively investigated cationic polymers for gene and drug delivery. Recently, great attention has been directed to design of carriers for co-delivery of nucleic acids and small molecules. These delivery systems are able to overcome the limitations of gene or drug delivery alone. The aim of this study is to prepare a targeted nano-carrier for co-delivery of doxorubicin (Dox) and gene using polyethylenimine.
Materials and Methods: In order to prepare the ligand-containing polymer conjugates, succinic anhydride was conjugated onto the hydroxyl group of Dox through an ester bond following the protection of Dox amines by Fmoc. Drug-polymer conjugates were then coupled with L-DOPA in order to prepare the targeted nanocarriers to the cells through Large Amino Acid Transporter-1 (LAT-1). The PEI derivatives were characterized using 1H-NMR. The toxicity of conjugated polymer, Dox and PEI was assessed on HepG2 and A375 cell lines with different expression level of LAT-1 transporters using MTT assay.
Results: The chemical structure of PEI conjugate was confirmed by 1H-NMR. The cytotoxicity measurement demonstrated a cell line-dependent toxicity profile at the concentrations tested in this study. It was shown that there was no significant difference in cell-induced toxicity between conjugated polymer and its parent form in A375 cell line while the cytotoxicity of conjugated polymer was significantly lower than the parent PEI in HepG2 cells.
Conclusion: These results provide promising evidence for further evaluation of PEI conjugate for co-delivery of drug and gene via LAT-1 transporters.


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