Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System

Thermostable exoshells (tES) are engineered proteinaceous nanoparticles used for the rapid encapsulation of therapeutic proteins/enzymes, whereby the nanoplatform protects the payload from proteases and other denaturants. Given the significance of oral delivery as the preferred model for drug admini...
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Gespeichert in:

Autor*in:	Samira Sadeghi [verfasserIn] Girish Vallerinteavide Mavelli [verfasserIn] Siddhesh Sujit Vaidya [verfasserIn] Chester Lee Drum [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	gastrointestinal thermostable exoshells DS-tES tES HRP rluc

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 23(2022), 17, p 9856
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:17, p 9856

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms23179856

Katalog-ID:	DOAJ023716010

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allfields	10.3390/ijms23179856 doi (DE-627)DOAJ023716010 (DE-599)DOAJc536db1c1a0d49bb8bc3addcb2490255 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Samira Sadeghi verfasserin aut Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Thermostable exoshells (tES) are engineered proteinaceous nanoparticles used for the rapid encapsulation of therapeutic proteins/enzymes, whereby the nanoplatform protects the payload from proteases and other denaturants. Given the significance of oral delivery as the preferred model for drug administration, we structurally improved the stability of tES through multiple inter-subunit disulfide linkages that were initially absent in the parent molecule. The disulfide-linked tES, as compared to tES, significantly stabilized the activity of encapsulated horseradish peroxidase (HRP) at acidic pH and against the primary human digestive enzymes, pepsin, and trypsin. Furthermore, the disulfide-linked tES (DS-tES) exhibited significant intestinal permeability as evaluated using Caco2 cells. In vivo bioluminescence assay showed that encapsulated Renilla luciferase (rluc) was ~3 times more stable in mice compared to the free enzyme. DS-tES collected mice feces had ~100 times more active enzyme in comparison to the control (free enzyme) after 24 h of oral administration, demonstrating strong intestinal stability. Taken together, the in vitro and in vivo results demonstrate the potential of DS-tES for intraluminal and systemic oral drug delivery applications. gastrointestinal thermostable exoshells DS-tES tES HRP rluc Biology (General) Chemistry Girish Vallerinteavide Mavelli verfasserin aut Siddhesh Sujit Vaidya verfasserin aut Chester Lee Drum verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 17, p 9856 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:17, p 9856 https://doi.org/10.3390/ijms23179856 kostenfrei https://doaj.org/article/c536db1c1a0d49bb8bc3addcb2490255 kostenfrei https://www.mdpi.com/1422-0067/23/17/9856 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 17, p 9856
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allfieldsGer	10.3390/ijms23179856 doi (DE-627)DOAJ023716010 (DE-599)DOAJc536db1c1a0d49bb8bc3addcb2490255 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Samira Sadeghi verfasserin aut Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Thermostable exoshells (tES) are engineered proteinaceous nanoparticles used for the rapid encapsulation of therapeutic proteins/enzymes, whereby the nanoplatform protects the payload from proteases and other denaturants. Given the significance of oral delivery as the preferred model for drug administration, we structurally improved the stability of tES through multiple inter-subunit disulfide linkages that were initially absent in the parent molecule. The disulfide-linked tES, as compared to tES, significantly stabilized the activity of encapsulated horseradish peroxidase (HRP) at acidic pH and against the primary human digestive enzymes, pepsin, and trypsin. Furthermore, the disulfide-linked tES (DS-tES) exhibited significant intestinal permeability as evaluated using Caco2 cells. In vivo bioluminescence assay showed that encapsulated Renilla luciferase (rluc) was ~3 times more stable in mice compared to the free enzyme. DS-tES collected mice feces had ~100 times more active enzyme in comparison to the control (free enzyme) after 24 h of oral administration, demonstrating strong intestinal stability. Taken together, the in vitro and in vivo results demonstrate the potential of DS-tES for intraluminal and systemic oral drug delivery applications. gastrointestinal thermostable exoshells DS-tES tES HRP rluc Biology (General) Chemistry Girish Vallerinteavide Mavelli verfasserin aut Siddhesh Sujit Vaidya verfasserin aut Chester Lee Drum verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 17, p 9856 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:17, p 9856 https://doi.org/10.3390/ijms23179856 kostenfrei https://doaj.org/article/c536db1c1a0d49bb8bc3addcb2490255 kostenfrei https://www.mdpi.com/1422-0067/23/17/9856 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 17, p 9856
allfieldsSound	10.3390/ijms23179856 doi (DE-627)DOAJ023716010 (DE-599)DOAJc536db1c1a0d49bb8bc3addcb2490255 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Samira Sadeghi verfasserin aut Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Thermostable exoshells (tES) are engineered proteinaceous nanoparticles used for the rapid encapsulation of therapeutic proteins/enzymes, whereby the nanoplatform protects the payload from proteases and other denaturants. Given the significance of oral delivery as the preferred model for drug administration, we structurally improved the stability of tES through multiple inter-subunit disulfide linkages that were initially absent in the parent molecule. The disulfide-linked tES, as compared to tES, significantly stabilized the activity of encapsulated horseradish peroxidase (HRP) at acidic pH and against the primary human digestive enzymes, pepsin, and trypsin. Furthermore, the disulfide-linked tES (DS-tES) exhibited significant intestinal permeability as evaluated using Caco2 cells. In vivo bioluminescence assay showed that encapsulated Renilla luciferase (rluc) was ~3 times more stable in mice compared to the free enzyme. DS-tES collected mice feces had ~100 times more active enzyme in comparison to the control (free enzyme) after 24 h of oral administration, demonstrating strong intestinal stability. Taken together, the in vitro and in vivo results demonstrate the potential of DS-tES for intraluminal and systemic oral drug delivery applications. gastrointestinal thermostable exoshells DS-tES tES HRP rluc Biology (General) Chemistry Girish Vallerinteavide Mavelli verfasserin aut Siddhesh Sujit Vaidya verfasserin aut Chester Lee Drum verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 17, p 9856 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:17, p 9856 https://doi.org/10.3390/ijms23179856 kostenfrei https://doaj.org/article/c536db1c1a0d49bb8bc3addcb2490255 kostenfrei https://www.mdpi.com/1422-0067/23/17/9856 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 17, p 9856
language	English
source	In International Journal of Molecular Sciences 23(2022), 17, p 9856 volume:23 year:2022 number:17, p 9856
sourceStr	In International Journal of Molecular Sciences 23(2022), 17, p 9856 volume:23 year:2022 number:17, p 9856
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authorswithroles_txt_mv	Samira Sadeghi @@aut@@ Girish Vallerinteavide Mavelli @@aut@@ Siddhesh Sujit Vaidya @@aut@@ Chester Lee Drum @@aut@@
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callnumber-first	Q - Science
author	Samira Sadeghi
spellingShingle	Samira Sadeghi misc QH301-705.5 misc QD1-999 misc gastrointestinal misc thermostable exoshells misc DS-tES misc tES misc HRP misc rluc misc Biology (General) misc Chemistry Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System
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topic_title	QH301-705.5 QD1-999 Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System gastrointestinal thermostable exoshells DS-tES tES HRP rluc
topic	misc QH301-705.5 misc QD1-999 misc gastrointestinal misc thermostable exoshells misc DS-tES misc tES misc HRP misc rluc misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc gastrointestinal misc thermostable exoshells misc DS-tES misc tES misc HRP misc rluc misc Biology (General) misc Chemistry
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title_full	Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System
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title_sort	gastrointestinal tract stabilized protein delivery using disulfide thermostable exoshell system
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title_auth	Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System
abstract	Thermostable exoshells (tES) are engineered proteinaceous nanoparticles used for the rapid encapsulation of therapeutic proteins/enzymes, whereby the nanoplatform protects the payload from proteases and other denaturants. Given the significance of oral delivery as the preferred model for drug administration, we structurally improved the stability of tES through multiple inter-subunit disulfide linkages that were initially absent in the parent molecule. The disulfide-linked tES, as compared to tES, significantly stabilized the activity of encapsulated horseradish peroxidase (HRP) at acidic pH and against the primary human digestive enzymes, pepsin, and trypsin. Furthermore, the disulfide-linked tES (DS-tES) exhibited significant intestinal permeability as evaluated using Caco2 cells. In vivo bioluminescence assay showed that encapsulated Renilla luciferase (rluc) was ~3 times more stable in mice compared to the free enzyme. DS-tES collected mice feces had ~100 times more active enzyme in comparison to the control (free enzyme) after 24 h of oral administration, demonstrating strong intestinal stability. Taken together, the in vitro and in vivo results demonstrate the potential of DS-tES for intraluminal and systemic oral drug delivery applications.
abstractGer	Thermostable exoshells (tES) are engineered proteinaceous nanoparticles used for the rapid encapsulation of therapeutic proteins/enzymes, whereby the nanoplatform protects the payload from proteases and other denaturants. Given the significance of oral delivery as the preferred model for drug administration, we structurally improved the stability of tES through multiple inter-subunit disulfide linkages that were initially absent in the parent molecule. The disulfide-linked tES, as compared to tES, significantly stabilized the activity of encapsulated horseradish peroxidase (HRP) at acidic pH and against the primary human digestive enzymes, pepsin, and trypsin. Furthermore, the disulfide-linked tES (DS-tES) exhibited significant intestinal permeability as evaluated using Caco2 cells. In vivo bioluminescence assay showed that encapsulated Renilla luciferase (rluc) was ~3 times more stable in mice compared to the free enzyme. DS-tES collected mice feces had ~100 times more active enzyme in comparison to the control (free enzyme) after 24 h of oral administration, demonstrating strong intestinal stability. Taken together, the in vitro and in vivo results demonstrate the potential of DS-tES for intraluminal and systemic oral drug delivery applications.
abstract_unstemmed	Thermostable exoshells (tES) are engineered proteinaceous nanoparticles used for the rapid encapsulation of therapeutic proteins/enzymes, whereby the nanoplatform protects the payload from proteases and other denaturants. Given the significance of oral delivery as the preferred model for drug administration, we structurally improved the stability of tES through multiple inter-subunit disulfide linkages that were initially absent in the parent molecule. The disulfide-linked tES, as compared to tES, significantly stabilized the activity of encapsulated horseradish peroxidase (HRP) at acidic pH and against the primary human digestive enzymes, pepsin, and trypsin. Furthermore, the disulfide-linked tES (DS-tES) exhibited significant intestinal permeability as evaluated using Caco2 cells. In vivo bioluminescence assay showed that encapsulated Renilla luciferase (rluc) was ~3 times more stable in mice compared to the free enzyme. DS-tES collected mice feces had ~100 times more active enzyme in comparison to the control (free enzyme) after 24 h of oral administration, demonstrating strong intestinal stability. Taken together, the in vitro and in vivo results demonstrate the potential of DS-tES for intraluminal and systemic oral drug delivery applications.
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title_short	Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System
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up_date	2024-07-03T19:06:37.834Z
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Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System

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