A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides

Ghullam Reza Barbari,1 Farid Abedin Dorkoosh,1 Mohsen Amini,2 Mohammad Sharifzadeh,3 Fateme Atyabi,1 Saeed Balalaie,4 Niyousha Rafiee Tehrani,5 Morteza Rafiee Tehrani1 1Department of Pharmaceutics, 2Department of Medicinal Chemistry, 3Department of Pharmacology, School of Pharmacy, Tehran Universit...

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Autores principales:	Barbari GR, Dorkoosh FA, Amini M, Sharifzadeh M, Atyabi F, Balalaei S, Rafiee Tehrani N, Rafiee Tehrani M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	ultra-small cell-penetrating peptide chitosan oral insulin nano-emulsion Caco-2 cell Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/024d1c7322464b5b98d42c1de6789e8c
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spelling	oai:doaj.org-article:024d1c7322464b5b98d42c1de6789e8c2021-12-02T03:58:28ZA novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides1178-2013https://doaj.org/article/024d1c7322464b5b98d42c1de6789e8c2017-05-01T00:00:00Zhttps://www.dovepress.com/a-novel-nanoemulsion-based-method-to-produce-ultrasmall-water-dispersi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ghullam Reza Barbari,1 Farid Abedin Dorkoosh,1 Mohsen Amini,2 Mohammad Sharifzadeh,3 Fateme Atyabi,1 Saeed Balalaie,4 Niyousha Rafiee Tehrani,5 Morteza Rafiee Tehrani1 1Department of Pharmaceutics, 2Department of Medicinal Chemistry, 3Department of Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, 4Department of Chemistry, Khaje Nasiroddin University, 5Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Abstract: A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O nanoemulsion serve as “nano-containers and nano-reactors”. The entrapped polymer chains of CS inside these “nano-reactors” are covalently cross-linked with the chains of polyethylene glycol (PEG), leading to rigidification and formation of NPs. These NPs possess excessive swelling properties in aqueous medium and preserve integrity in all pH ranges due to chemical cross-linking with PEG. A potent and newly developed cell-penetrating peptide (CPP) is further chemically conjugated to the surface of the NPs, leading to development of a novel peptide-conjugated derivative of CS with profound tight-junction opening properties. The CPP-conjugated NPs can easily be loaded with almost all kinds of proteins, peptides and nucleotides for oral delivery applications. Feasibility of this nanoparticulate system for oral delivery of a model peptide (insulin) is investigated in Caco-2 cell line. The cell culture results for translocation of insulin across the cell monolayer are very promising (15%–19% increase), and animal studies are actively under progress and will be published separately. Keywords: ultrasmall, cell-penetrating peptide, chitosan, oral insulin, nanoemulsion, Caco-2 cellBarbari GRDorkoosh FAAmini MSharifzadeh MAtyabi FBalalaei SRafiee Tehrani NRafiee Tehrani MDove Medical Pressarticleultra-smallcell-penetrating peptidechitosanoral insulinnano-emulsionCaco-2 cellMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3471-3483 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	ultra-small cell-penetrating peptide chitosan oral insulin nano-emulsion Caco-2 cell Medicine (General) R5-920
spellingShingle	ultra-small cell-penetrating peptide chitosan oral insulin nano-emulsion Caco-2 cell Medicine (General) R5-920 Barbari GR Dorkoosh FA Amini M Sharifzadeh M Atyabi F Balalaei S Rafiee Tehrani N Rafiee Tehrani M A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides
description	Ghullam Reza Barbari,1 Farid Abedin Dorkoosh,1 Mohsen Amini,2 Mohammad Sharifzadeh,3 Fateme Atyabi,1 Saeed Balalaie,4 Niyousha Rafiee Tehrani,5 Morteza Rafiee Tehrani1 1Department of Pharmaceutics, 2Department of Medicinal Chemistry, 3Department of Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, 4Department of Chemistry, Khaje Nasiroddin University, 5Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Abstract: A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O nanoemulsion serve as “nano-containers and nano-reactors”. The entrapped polymer chains of CS inside these “nano-reactors” are covalently cross-linked with the chains of polyethylene glycol (PEG), leading to rigidification and formation of NPs. These NPs possess excessive swelling properties in aqueous medium and preserve integrity in all pH ranges due to chemical cross-linking with PEG. A potent and newly developed cell-penetrating peptide (CPP) is further chemically conjugated to the surface of the NPs, leading to development of a novel peptide-conjugated derivative of CS with profound tight-junction opening properties. The CPP-conjugated NPs can easily be loaded with almost all kinds of proteins, peptides and nucleotides for oral delivery applications. Feasibility of this nanoparticulate system for oral delivery of a model peptide (insulin) is investigated in Caco-2 cell line. The cell culture results for translocation of insulin across the cell monolayer are very promising (15%–19% increase), and animal studies are actively under progress and will be published separately. Keywords: ultrasmall, cell-penetrating peptide, chitosan, oral insulin, nanoemulsion, Caco-2 cell
format	article
author	Barbari GR Dorkoosh FA Amini M Sharifzadeh M Atyabi F Balalaei S Rafiee Tehrani N Rafiee Tehrani M
author_facet	Barbari GR Dorkoosh FA Amini M Sharifzadeh M Atyabi F Balalaei S Rafiee Tehrani N Rafiee Tehrani M
author_sort	Barbari GR
title	A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides
title_short	A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides
title_full	A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides
title_fullStr	A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides
title_full_unstemmed	A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides
title_sort	novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/024d1c7322464b5b98d42c1de6789e8c
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A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides

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