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...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-10-01
|
Series: | Pharmaceutics |
Subjects: | |
Online Access: | https://www.mdpi.com/1999-4923/11/10/532 |
_version_ | 1798024471086366720 |
---|---|
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 ζ-potential values (−45, −43 and −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. |
first_indexed | 2024-04-11T18:04:08Z |
format | Article |
id | doaj.art-574e7feb2e4a402b836c3e498d611ffc |
institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
last_indexed | 2024-04-11T18:04:08Z |
publishDate | 2019-10-01 |
publisher | MDPI AG |
record_format | Article |
series | Pharmaceutics |
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 ζ-potential values (−45, −43 and −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 |
work_keys_str_mv | AT elitamontanari intracellulardeliveryofnaturalantioxidantsviahyaluronannanohydrogels AT chiaradimeo intracellulardeliveryofnaturalantioxidantsviahyaluronannanohydrogels AT tommasinacoviello intracellulardeliveryofnaturalantioxidantsviahyaluronannanohydrogels AT virginiegueguen intracellulardeliveryofnaturalantioxidantsviahyaluronannanohydrogels AT gracielapavondjavid intracellulardeliveryofnaturalantioxidantsviahyaluronannanohydrogels AT pietromatricardi intracellulardeliveryofnaturalantioxidantsviahyaluronannanohydrogels |