Intracellular Delivery of Natural Antioxidants via Hyaluronan Nanohydrogels

Natural antioxidants, such as astaxanthin (AX), resveratrol (RV) and curcumin (CU), are bioactive molecules that show a number of therapeutic effects. However, their applications are remarkably limited by their poor water solubility, physico-chemical instability and low bioavailability. In the prese...

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Main Authors: Elita Montanari, Chiara Di Meo, Tommasina Coviello, Virginie Gueguen, Graciela Pavon-Djavid, Pietro Matricardi
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/11/10/532
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author Elita Montanari
Chiara Di Meo
Tommasina Coviello
Virginie Gueguen
Graciela Pavon-Djavid
Pietro Matricardi
author_facet Elita Montanari
Chiara Di Meo
Tommasina Coviello
Virginie Gueguen
Graciela Pavon-Djavid
Pietro Matricardi
author_sort Elita Montanari
collection DOAJ
description Natural antioxidants, such as astaxanthin (AX), resveratrol (RV) and curcumin (CU), are bioactive molecules that show a number of therapeutic effects. However, their applications are remarkably limited by their poor water solubility, physico-chemical instability and low bioavailability. In the present work, it is shown that self-assembled hyaluronan (HA)-based nanohydrogels (NHs) are taken up by endothelial cells (Human Umbilical Vein Endothelial Cells, HUVECs), preferentially accumulating in the perinuclear area of oxidatively stressed HUVECs, as evidenced by flow cytometry and confocal microscopy analyses. Furthermore, NHs are able to physically entrap and to significantly enhance the apparent water solubility of AX, RV and CU in aqueous media. AX/NHs, RV/NHs and CU/NHs systems showed good hydrodynamic diameters (287, 214 and 267 nm, respectively), suitable &#950;-potential values (&#8722;45, &#8722;43 and &#8722;37 mV, respectively) and the capability to neutralise reactive oxygen species (ROS) in tube. AX/NHs system was also able to neutralise ROS <i>in vitro</i> and did not show any toxicity against HUVECs. This research suggests that HA-based NHs can represent a kind of nano-carrier suitable for the intracellular delivery of antioxidant agents, for the treatment of oxidative stress in endothelial cells.
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spelling doaj.art-574e7feb2e4a402b836c3e498d611ffc2022-12-22T04:10:23ZengMDPI AGPharmaceutics1999-49232019-10-01111053210.3390/pharmaceutics11100532pharmaceutics11100532Intracellular Delivery of Natural Antioxidants via Hyaluronan NanohydrogelsElita Montanari0Chiara Di Meo1Tommasina Coviello2Virginie Gueguen3Graciela Pavon-Djavid4Pietro Matricardi5Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyINSERM U1148, Laboratory for Vascular Translational Science, Cardiovascular Bioengineering, Paris 13 University, Sorbonne Paris Cite 99, Av. Jean-Baptiste Clément, 93430 Villetaneuse, FranceINSERM U1148, Laboratory for Vascular Translational Science, Cardiovascular Bioengineering, Paris 13 University, Sorbonne Paris Cite 99, Av. Jean-Baptiste Clément, 93430 Villetaneuse, FranceDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyNatural antioxidants, such as astaxanthin (AX), resveratrol (RV) and curcumin (CU), are bioactive molecules that show a number of therapeutic effects. However, their applications are remarkably limited by their poor water solubility, physico-chemical instability and low bioavailability. In the present work, it is shown that self-assembled hyaluronan (HA)-based nanohydrogels (NHs) are taken up by endothelial cells (Human Umbilical Vein Endothelial Cells, HUVECs), preferentially accumulating in the perinuclear area of oxidatively stressed HUVECs, as evidenced by flow cytometry and confocal microscopy analyses. Furthermore, NHs are able to physically entrap and to significantly enhance the apparent water solubility of AX, RV and CU in aqueous media. AX/NHs, RV/NHs and CU/NHs systems showed good hydrodynamic diameters (287, 214 and 267 nm, respectively), suitable &#950;-potential values (&#8722;45, &#8722;43 and &#8722;37 mV, respectively) and the capability to neutralise reactive oxygen species (ROS) in tube. AX/NHs system was also able to neutralise ROS <i>in vitro</i> and did not show any toxicity against HUVECs. This research suggests that HA-based NHs can represent a kind of nano-carrier suitable for the intracellular delivery of antioxidant agents, for the treatment of oxidative stress in endothelial cells.https://www.mdpi.com/1999-4923/11/10/532drug deliveryastaxanthinresveratrolcurcuminhyaluronannanohydrogelsoxidative stressintracellular therapy
spellingShingle Elita Montanari
Chiara Di Meo
Tommasina Coviello
Virginie Gueguen
Graciela Pavon-Djavid
Pietro Matricardi
Intracellular Delivery of Natural Antioxidants via Hyaluronan Nanohydrogels
Pharmaceutics
drug delivery
astaxanthin
resveratrol
curcumin
hyaluronan
nanohydrogels
oxidative stress
intracellular therapy
title Intracellular Delivery of Natural Antioxidants via Hyaluronan Nanohydrogels
title_full Intracellular Delivery of Natural Antioxidants via Hyaluronan Nanohydrogels
title_fullStr Intracellular Delivery of Natural Antioxidants via Hyaluronan Nanohydrogels
title_full_unstemmed Intracellular Delivery of Natural Antioxidants via Hyaluronan Nanohydrogels
title_short Intracellular Delivery of Natural Antioxidants via Hyaluronan Nanohydrogels
title_sort intracellular delivery of natural antioxidants via hyaluronan nanohydrogels
topic drug delivery
astaxanthin
resveratrol
curcumin
hyaluronan
nanohydrogels
oxidative stress
intracellular therapy
url https://www.mdpi.com/1999-4923/11/10/532
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