Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(Propyleneimine) nanocarriers for gene delivery#

Malaekeh-Nikouei, B. and Rezaee, M. and Gholami, L. and Mousavi, N. S. and Oskuee, R. K. (2018) Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(Propyleneimine) nanocarriers for gene delivery#. Pharmaceutical Biology, 56 (1). pp. 519-527.

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Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(Propyleneimine) nanocarriers for gene delivery.pdf

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Abstract

Context: Polypropylenimine (PPI), a cationic dendrimer with defined structure and positive surface charge, is a potent non-viral vector. Dexamethasone (Dexa) conveys to the nucleus through interaction with its intracellular receptor. Objective: This study develops efficient and non-toxic gene carriers through conjugation of Dexa at various percentages (5, 10 and 20) to the fourth and the fifth generation PPIs (PPIG4s and PPIG5s). Materials and methods: The 21-OH group of Dexa (0.536 mmol) was modified with methanesulfonyl chloride (0.644 mmol) to activate it (Dexa-mesylate), and then it was conjugated to PPIs using Traut’s reagent. After dialysis (48 h) and lyophilization, the physicochemical characteristics of products (PPI-Dexa) including zeta potential, size, buffering capacity and DNA condensing capability were investigated and compared with unmodified PPIs. Moreover, the cytotoxicity and transfection activity of the Dexa-modified PPIs were assessed using Neuro2A cells. Results: Transfection of PPIG4 was close to PEI 25 kDa. Although the addition of Dexa to PPIG4s did not improve their transfection, their cytotoxicity was improved; especially in the carrier to DNA weight ratios (C/P) of one and two. The Dexa conjugation to PPIG5s enhanced their transfection at C/P ratio of one in both 5 (1.3-fold) and 10 (1.6-fold) Dexa grafting, of which the best result was observed in PPIG5-Dexa 10 at C/P ratio of one. Discussion and conclusions: The modification of PPIs with Dexa is a promising approach to improve their cytotoxicity and transfection. The higher optimization of physicochemical characteristics, the better cell transfection and toxicity will be achieved. © 2018 The Author(s).

Item Type: Article
Additional Information: Cited By :1 Export Date: 16 February 2020 CODEN: PHBIF Correspondence Address: Oskuee, R.K.; Faculty of Medicine, Mashhad University of Medical Sciences, P.O. Box 8564-917794, Iran; email: oskueekr@mums.ac.ir
Uncontrolled Keywords: Dendrimers Gene transfer techniques Non-viral vectors Nuclear localization signals Polyplexes 2 iminothiolane azetidine derivative chloride dexamethasone mesylic acid methanesulfonyl chloride nanocarrier plasmid DNA poly(propyleneimine) unclassified drug antiinflammatory agent nanoparticle polypropylene Article chemical modification complex formation concentration (parameter) conjugation controlled study cytotoxicity dialysis DNA structure DNA transfection freeze drying Neuro-2a cell line nonviral gene delivery system particle size physical chemistry process optimization structure analysis synthesis zeta potential chemistry gene transfer genetic transfection human procedures standards Anti-Inflammatory Agents Humans Nanoparticles Polypropylenes Transfection
Subjects: QV pharmacology
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 11 May 2020 03:50
Last Modified: 11 May 2020 03:50
URI: http://eprints.mums.ac.ir/id/eprint/17382

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