Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity

Saba Naqvi, Harish Sharma, Swaran JS Flora Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-Raebareli), Lucknow 226002, IndiaCorrespondence: Swaran JS Flora; Saba NaqviDepartment of Pharmacology & Toxicology, National Institu...

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Autores principales:	Naqvi S, Sharma H, Flora SJS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	quercetin ormosil nanoparticles cyclophosphamide hepatoprotection lactobionic acid. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8ec118fc35044f7693be38e94acbcdb4
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spelling	oai:doaj.org-article:8ec118fc35044f7693be38e94acbcdb42021-12-02T05:11:25ZLactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity1178-2013https://doaj.org/article/8ec118fc35044f7693be38e94acbcdb42019-11-01T00:00:00Zhttps://www.dovepress.com/lactobionic-acid-conjugated-quercetin-loaded-organically-modified-sili-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Saba Naqvi, Harish Sharma, Swaran JS Flora Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-Raebareli), Lucknow 226002, IndiaCorrespondence: Swaran JS Flora; Saba NaqviDepartment of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-Raebareli), Bijnor-Sisendi Road, Lucknow, UP 226002, IndiaTel +91 9425482305; Tel +91 9411836483Email director@niperraebareli.edu.in; writetosaba@yahoo.comObjective: The study was designed to investigate the therapeutic potential of lactobionic acid (LA) conjugated quercetin (Q) loaded organically modified silica nanoparticles (LA-Q-ORMOSIL) with bulk quercetin to mitigate cyclophosphamide (CP) induced liver injury.Methodology: Q-ORMOSIL nanoparticles were synthesized and characterized using UV-Vis spectroscopy, TEM, Zeta sizer, FTIR and EDX. Further, encapsulation efficiency and in vitro release kinetic study was done. Q-ORMOSIL nanoparticles surface were modified with lactobionic acid, a ligand for the asialoglycoprotein receptor on the hepatocyte surface. The hepatoprotective effects of Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles were evaluated in vivo. Cyclophosphamide (20 mg/kg/day, i.p) was co-administered for seven days with bulk quercetin (50mg/kg/day) and quercetin nanoparticles (50μg/kg/day). After seven days, the number of biomarkers for liver function test and oxidative stress were determined in liver homogenate. Histopathological changes were also analyzed in control and treated liver tissues.Results: Physiochemical characterization of LA-Q-ORMOSIL nanoparticles depicts that the particles formed were of approx. 80 nm, spherical, monodispersed in nature and showed sustain drug release in in vitro study. Our results further suggested that Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles significantly decreased tissue TBARS, ROS levels and ALT, AST, and ALP activities compared to CP induced group. On the other hand, tissue antioxidant levels (GSH, GST, and catalase) showed a significant increase in LA-Q-ORMOSIL treated group compared to the CP treated group confirming its high therapeutic efficacy during liver injury.Conclusion: Targeted nanoquercetin demonstrated a significant hepatoprotective effect compared to bulk quercetin against CP-induced hepatotoxicity and it considerably reduced bulk quercetin dose level to many folds. Bulk quercetin has low bioavailability and thus, from obtained data we suggest that LA-Q-ORMOSIL nanoparticles provide high therapeutic value in protecting experimental animals against CP-induced liver injury. We also propose multifunctional dye-doped LA-modified ORMOSIL nanoparticles for future studies in facilitating nanoparticles uptake to hepatocytes for liver diagnosis and treatment.Keywords: quercetin, ORMOSIL nanoparticles, cyclophosphamide, hepatoprotection, lactobionic acidNaqvi SSharma HFlora SJSDove Medical Pressarticlequercetinormosil nanoparticlescyclophosphamidehepatoprotectionlactobionic acid.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8943-8959 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	quercetin ormosil nanoparticles cyclophosphamide hepatoprotection lactobionic acid. Medicine (General) R5-920
spellingShingle	quercetin ormosil nanoparticles cyclophosphamide hepatoprotection lactobionic acid. Medicine (General) R5-920 Naqvi S Sharma H Flora SJS Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity
description	Saba Naqvi, Harish Sharma, Swaran JS Flora Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-Raebareli), Lucknow 226002, IndiaCorrespondence: Swaran JS Flora; Saba NaqviDepartment of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-Raebareli), Bijnor-Sisendi Road, Lucknow, UP 226002, IndiaTel +91 9425482305; Tel +91 9411836483Email director@niperraebareli.edu.in; writetosaba@yahoo.comObjective: The study was designed to investigate the therapeutic potential of lactobionic acid (LA) conjugated quercetin (Q) loaded organically modified silica nanoparticles (LA-Q-ORMOSIL) with bulk quercetin to mitigate cyclophosphamide (CP) induced liver injury.Methodology: Q-ORMOSIL nanoparticles were synthesized and characterized using UV-Vis spectroscopy, TEM, Zeta sizer, FTIR and EDX. Further, encapsulation efficiency and in vitro release kinetic study was done. Q-ORMOSIL nanoparticles surface were modified with lactobionic acid, a ligand for the asialoglycoprotein receptor on the hepatocyte surface. The hepatoprotective effects of Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles were evaluated in vivo. Cyclophosphamide (20 mg/kg/day, i.p) was co-administered for seven days with bulk quercetin (50mg/kg/day) and quercetin nanoparticles (50μg/kg/day). After seven days, the number of biomarkers for liver function test and oxidative stress were determined in liver homogenate. Histopathological changes were also analyzed in control and treated liver tissues.Results: Physiochemical characterization of LA-Q-ORMOSIL nanoparticles depicts that the particles formed were of approx. 80 nm, spherical, monodispersed in nature and showed sustain drug release in in vitro study. Our results further suggested that Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles significantly decreased tissue TBARS, ROS levels and ALT, AST, and ALP activities compared to CP induced group. On the other hand, tissue antioxidant levels (GSH, GST, and catalase) showed a significant increase in LA-Q-ORMOSIL treated group compared to the CP treated group confirming its high therapeutic efficacy during liver injury.Conclusion: Targeted nanoquercetin demonstrated a significant hepatoprotective effect compared to bulk quercetin against CP-induced hepatotoxicity and it considerably reduced bulk quercetin dose level to many folds. Bulk quercetin has low bioavailability and thus, from obtained data we suggest that LA-Q-ORMOSIL nanoparticles provide high therapeutic value in protecting experimental animals against CP-induced liver injury. We also propose multifunctional dye-doped LA-modified ORMOSIL nanoparticles for future studies in facilitating nanoparticles uptake to hepatocytes for liver diagnosis and treatment.Keywords: quercetin, ORMOSIL nanoparticles, cyclophosphamide, hepatoprotection, lactobionic acid
format	article
author	Naqvi S Sharma H Flora SJS
author_facet	Naqvi S Sharma H Flora SJS
author_sort	Naqvi S
title	Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity
title_short	Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity
title_full	Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity
title_fullStr	Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity
title_full_unstemmed	Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity
title_sort	lactobionic acid conjugated quercetin loaded organically modified silica nanoparticles mitigates cyclophosphamide induced hepatocytotoxicity
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/8ec118fc35044f7693be38e94acbcdb4
work_keys_str_mv	AT naqvis lactobionicacidconjugatedquercetinloadedorganicallymodifiedsilicananoparticlesmitigatescyclophosphamideinducedhepatocytotoxicity AT sharmah lactobionicacidconjugatedquercetinloadedorganicallymodifiedsilicananoparticlesmitigatescyclophosphamideinducedhepatocytotoxicity AT florasjs lactobionicacidconjugatedquercetinloadedorganicallymodifiedsilicananoparticlesmitigatescyclophosphamideinducedhepatocytotoxicity
_version_	1718400542763384832

Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity

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