Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as efficient gene delivery vectors

Moghadam Ariaee, Faezeh and Hashemi, Maryam and Amel Farzad, Sara and Abnous, Khalil and Ramezani, Mohammad (2016) Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as efficient gene delivery vectors. Iranian Journal of Basic Medical Sciences, 19 (10). pp. 1096-1104.

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Abstract

Objective(s): First, 10-bromodecanoic acid was covalently attached to all available surface primary amines of PPI G2 and G3 to increase their lipophilicity. In the subsequent step, PPIs were conjugated to the alkylcarboxylate groups of alkylcarboxylate-PPI derivatives to increase the number of surface primary amines. Physicochemical properties of modified PPIs were determined. Transfection experiments (using both luciferase and green fluorescent protein (GFP)- expressing plasmids) and cytotoxicity assay were performed to evaluate the efficiency of the final derivatives. Materials and Methods: First, 10-bromodecanoic acid was covalently attached to all available surface primary amines of PPI G2 and G3 to increase their lipophilicity. In the subsequent step, PPIs were conjugated to the alkylcarboxylate groups of alkylcarboxylate-PPI derivatives to increase the number of surface primary amines. Physicochemical properties of modified PPIs were determined. Transfection experiments (using both luciferase and green fluorescent protein (GFP)- expressing plasmids) and cytotoxicity assay were performed to evaluate the efficiency of the final derivatives. Results: Fabricated vectors condensed DNA effectively so that polyplexes with appropriate size (below 155 nm) and positive surface charge were constructed. Cross-linked low molecular weight PPIs (G2 or G3) with decanoate linkage increased transfection efficiency significantly while maintaining the low cytotoxicity. PPI G2 derivative exhibited increased buffering capacity which is believed to be responsible for better proton sponge mechanism leading to higher transfection efficiency. Conclusion: Our results indicated that oligomerization of low molecular weight PPI (PPI G2-alkyl-PPI G2 conjugate) could be an approach to increase the transfection efficiency and to lower the cytotoxicity of low molecular weight polycations.

Item Type: Article
Subjects: QV pharmacology
Divisions: Journals > Iranian J Basic Medical Sciences
Depositing User: ijbms ijbms
Date Deposited: 27 Sep 2017 15:16
Last Modified: 27 Sep 2017 15:16
URI: http://eprints.mums.ac.ir/id/eprint/5301

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