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|Title:||Folic acid-conjugated depolymerized quaternized chitosan as potential targeted gene delivery vector|
|Abstract:||Ligand-conjugated delivery vectors that target over-expressed cell surface receptors have a potential impact on gene therapy. In the study reported, high-molecular-weight chitosan was depolymerized to medium and low molecular weight and trimethylated to render the polymer soluble over a wider pH range. Folate conjugation was introduced to the quartemized derivative to improve gene transfection efficiency. Complexes of the folic acid-conjugated trimethylated depolymerized chitosan (FTMC) with plasmid DNA (pDNA) formed core-shell nanostructured particles. Gel electrophoretic band retardation showed efficient condensation of DNA. These derivatives and their complexes with pDNA were tested for toxicity and haemocompatibility and were found to be significantly less toxic and haemocompatible than polyethyleneimine. Transfection efficiency and nuclear uptake properties were tested in the human KB oral epidermoid cell line, which over-expresses the folate receptor in the presence of 10% serum. Among the four FTMC derivatives investigated, folic acid-conjugated chitosan having low molecular weight and medium folate conjugation was found to be a potential vector for gene delivery applications with good transfection and nuclear uptake properties, as proved by YOYO labelling of pDNA. (C) 2011 Society of Chemical Industry|
|Appears in Collections:||Journal Articles|
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