Stealth cross-linked polymeric nanoparticles for passive drug targeting: a combination of molecular docking and comprehe
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Bull Mater Sci (2020)43:232 https://doi.org/10.1007/s12034-020-02166-8
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Stealth cross-linked polymeric nanoparticles for passive drug targeting: a combination of molecular docking and comprehensive in vitro assay ABBAS HEMATI AZANDARYANI1,2, SOHEILA KASHANIAN1,2,*, YADOLLAH BAHRAMI3,4,5, MOHSEN SHAHLAEI2, KATAYOUN DERAKHSHANDEH6 and SAJAD MORADI2 1
Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah 6714414971, Iran Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran 3 Department of Medical Biotechnology, School of Medicine, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia 4 Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran 5 Molecular Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran 6 Department of Pharmaceutics, Faculty of Pharmacy, Hamedan University of Medical Sciences, Hamedan 6517838678, Iran *Author for correspondence ([email protected]) 2
MS received 7 February 2019; accepted 19 March 2020 Abstract. Till date, several studies have reported magnetic drug targeting as well as passive drug delivery. In this study, the passive characteristic of PEGylated carriers with a neutral surface charge rather than chitosan (CS)-based nanoparticles (NPs) with a positive charge was proved using molecular docking. The complete and without flaw stealth CS-coated magnetic NPs (mNPs) loaded with an anticancer drug for intravenous drug delivery were prepared using a modified ioniccrosslinking method. The physicochemical properties of the prepared magnetic-CS NPs were characterized in detail. The transmission electron micrographs of NPs showed an uniform particle morphology with an average diameter of smaller than 10 nm. The average IC50 values of the drug in PEGylated NPs for MCF-7 and PC-12 cells were 44 and 72 lM, respectively. The fabricated stealth NPs can increase the cytotoxicity and cell permeability of formulation that may release the entire drug in targeted shape to objective tissues that were firstly proved by molecular docking. This strategy showed a reduction in uptaking of mNPs by the reticuloendothelial system, which indeed increases the concentration of therapeutic agent(s) in the target site. Keywords. Chitosan; targeted drug delivery; passive drug delivery; PEGylation; ex vivo study; carbohydrate recognition domains.
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Introduction
Tumour-targeted drug delivery has been applied to treat just cancerous tissues, due to the high cytotoxicity of anticancer drugs compared to normal ones. These systems can improve the efficacy of chemotherapy agents whereas decrease the systemic cytotoxicity of these drugs to cancerous tissue [1,2]. Inorganic/organic nanoparticles (NPs) play a significant role in drug delivery applications owing to their submicron sizes. It has been reported th
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