Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links

Samira Sadat Abolmaali,1 Ali Tamaddon,1,2 Gholamhossein Yousefi,1,2 Katayoun Javidnia,3 Rasoul Dinarvand41Department of Pharmaceutics, Shiraz School of Pharmacy, 2Center for Nanotechnology in Drug Delivery, 3Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Scie...

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Autores principales:	Abolmaali SS, Tamaddon A, Yousefi G, Javidnia K, Dinarv, R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/293cd2c4b591489da44e4a6c6cc0ee7b
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spelling	oai:doaj.org-article:293cd2c4b591489da44e4a6c6cc0ee7b2021-12-02T05:36:18ZSequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links1178-2013https://doaj.org/article/293cd2c4b591489da44e4a6c6cc0ee7b2014-06-01T00:00:00Zhttp://www.dovepress.com/sequential-optimization-of-methotrexate-encapsulation-in-micellar-nano-a17132https://doaj.org/toc/1178-2013 Samira Sadat Abolmaali,1 Ali Tamaddon,1,2 Gholamhossein Yousefi,1,2 Katayoun Javidnia,3 Rasoul Dinarvand41Department of Pharmaceutics, Shiraz School of Pharmacy, 2Center for Nanotechnology in Drug Delivery, 3Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; 4Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranAbstract: A functional polycation nanonetwork was developed for delivery of water soluble chemotherapeutic agents. The complexes of polyethyleneimine grafted methoxy polyethylene glycol (PEI-g-mPEG) and Zn2+ were utilized as the micellar template for cross-linking with dithiodipropionic acid, followed by an acidic pH dialysis to remove the metal ion from the micellar template. The synthesis method was optimized according to pH, the molar ratio of Zn2+, and the cross-link ratio. The atomic force microscopy showed soft, discrete, and uniform nano-networks. They were sensitive to the simulated reductive environment as determined by Ellman's assay. They showed few positive ζ potential and an average hydrodynamic diameter of 162±10 nm, which decreased to 49±11 nm upon dehydration. The ionic character of the nano-networks allowed the achievement of a higher-loading capacity of methotrexate (MTX), approximately 57% weight per weight, depending on the cross-link and the drug feed ratios. The nano-networks actively loaded with MTX presented some suitable properties, such as the hydrodynamic size of 117±16 nm, polydispersity index of 0.22, and a prolonged swelling-controlled release profile over 24 hours that boosted following reductive activation of the nanonetwork biodegradation. Unlike the PEI ionomer, the nano-networks provided an acceptable cytotoxicity profile. The drug-loaded nano-networks exhibited more specific cytotoxicity against human hepatocellular carcinoma cells if compared to free MTX at concentrations above 1 µM. The enhanced antitumor activity in vitro might be attributed to endocytic entry of MTX-loaded nano-networks that was found in the epifluorescence microscopy experiment for the fluorophore-labeled nano-networks.Keywords: nanonetwork, polyethyleneimine, ionomer complex, template assisted synthesis, methotrexate, cytotoxicityAbolmaali SSTamaddon AYousefi GJavidnia KDinarvRDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2833-2848 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Abolmaali SS Tamaddon A Yousefi G Javidnia K Dinarv R Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links
description	Samira Sadat Abolmaali,1 Ali Tamaddon,1,2 Gholamhossein Yousefi,1,2 Katayoun Javidnia,3 Rasoul Dinarvand41Department of Pharmaceutics, Shiraz School of Pharmacy, 2Center for Nanotechnology in Drug Delivery, 3Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; 4Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranAbstract: A functional polycation nanonetwork was developed for delivery of water soluble chemotherapeutic agents. The complexes of polyethyleneimine grafted methoxy polyethylene glycol (PEI-g-mPEG) and Zn2+ were utilized as the micellar template for cross-linking with dithiodipropionic acid, followed by an acidic pH dialysis to remove the metal ion from the micellar template. The synthesis method was optimized according to pH, the molar ratio of Zn2+, and the cross-link ratio. The atomic force microscopy showed soft, discrete, and uniform nano-networks. They were sensitive to the simulated reductive environment as determined by Ellman's assay. They showed few positive ζ potential and an average hydrodynamic diameter of 162±10 nm, which decreased to 49±11 nm upon dehydration. The ionic character of the nano-networks allowed the achievement of a higher-loading capacity of methotrexate (MTX), approximately 57% weight per weight, depending on the cross-link and the drug feed ratios. The nano-networks actively loaded with MTX presented some suitable properties, such as the hydrodynamic size of 117±16 nm, polydispersity index of 0.22, and a prolonged swelling-controlled release profile over 24 hours that boosted following reductive activation of the nanonetwork biodegradation. Unlike the PEI ionomer, the nano-networks provided an acceptable cytotoxicity profile. The drug-loaded nano-networks exhibited more specific cytotoxicity against human hepatocellular carcinoma cells if compared to free MTX at concentrations above 1 µM. The enhanced antitumor activity in vitro might be attributed to endocytic entry of MTX-loaded nano-networks that was found in the epifluorescence microscopy experiment for the fluorophore-labeled nano-networks.Keywords: nanonetwork, polyethyleneimine, ionomer complex, template assisted synthesis, methotrexate, cytotoxicity
format	article
author	Abolmaali SS Tamaddon A Yousefi G Javidnia K Dinarv R
author_facet	Abolmaali SS Tamaddon A Yousefi G Javidnia K Dinarv R
author_sort	Abolmaali SS
title	Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links
title_short	Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links
title_full	Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links
title_fullStr	Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links
title_full_unstemmed	Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links
title_sort	sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/293cd2c4b591489da44e4a6c6cc0ee7b
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Sequential optimization of methotrexate encapsulation in micellar nano-networks of polyethyleneimine ionomer containing redox-sensitive cross-links

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