|
KMID : 1146920190490010105
|
|
Journal of Pharmaceutical Investigation
2019 Volume.49 No. 1 p.105 ~ p.114
|
|
|
Charge reduction: an efficient strategy to reduce toxicity and increase the transfection efficiency of high molecular weight polyethylenimine
|
|
Rezaee Mehdi
Gholami Leila
Gildeh Mojtaba Seddighi
Ramezani Mohammad
Oskuee Reza Kazemi
|
|
|
Abstract
|
|
|
|
With high potency in treatment of various diseases, gene therapy is mainly hindered by lack of safe and efficient gene delivery vectors. The current study was aimed to develop an efficient non-viral vector with adequate cytotoxicity. To this end, alkylcarboxylate chains (6C, 10C, 16C) were exploited to ameliorate the characteristics of PEI 750 kDa. Briefly, alkylcarboxylate chains with three different lengths (6C, 10C, 16C) were chemically grafted to the primary amine groups of PEI 750 kDa in three percentages (10, 50, and 100%). After evaluating the physicochemical properties of prepared vectors including surface charge, size, buffering capacity, and DNA condensing, their transfection efficiency and cytotoxicity were investigated in Neuro2A cells. The polyplexes size were 158.9?264.5 nm and their zeta potentials were 14?30 mV, while their buffering capacity and DNA condensing were not significantly decreased. The highest transfection efficiency in term of C/P ratio was observed in PEI750-10C-68%, PEI750-10C-7%, and PEI750-6C-7% at C/P ratios of 2, 4, and 6, respectively. Altogether, the decanoylcarboxylate-modified PEI with medium grafting percentages showed promising results as gene delivery vector. To sum up, the modification of high molecular weight PEIs by alkylcarboxylate chains is an efficient approach for development of more efficient non-viral vectors.
|
|
|
KEYWORD
|
|
|
Alkylcarboxylate chains, Gene delivery, Non-viral vectors, Polyethylenimine, Polyplexes
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
|
|