N-Diethylmethyl chitosan for gene delivery to pancreatic cancer cells and the relation between charge ratio and biologic properties of polyplexes via interpolations polynomial

Abstract

In gene therapy of pancreatic cancer, non-viral vectors show an important role. These vectors are modified with the aim of improvement for pancreatic cancer gene therapy. For this aim, we used N,N-diethyl N-methyl chitosan (DEMC) for gene delivery to human pancreatic cancer cells (A5PC-1). pEGFP (Enhanced green fluorescent protein plasmid) was used as a model plasmid. In order to evaluate the efficiency of this polymer for gene delivery, the DEMC/pEGFP complexes are characterized via photon correlation spectroscopy, gel electrophoresis, fluorescence microscopy, flow cytometry and MTT assay. Also cancer cells' mean fluorescence intensity (MFI) and size changes after transfection are evaluated. The enhancement in polyplexes' charge ratios from 5 to 40, results in 16.70-fold increase in transfection efficiency. Higher MFI, cell size and cytotoxicity were observed as the N/P ratio increased. Considering that mathematical models can be used to understand and predict consequences associated with nanomedicine, the relation between DEMC/pDNA complexes charge ratio, cell transfection and toxicity was evaluated for the first time with Lagrange's interpolation polynomial method. (c) 2011 Elsevier B.V. All rights reserved.