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Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells

Thymoquinone (TQ) is the main constituent of Nigella sativa L. essential oil. In vitro studies have shown its protective effect against H(2)O(2)-induced oxidative stress in human retinal pigment epithelium cells, and in vivo experiments have demonstrated its effect in decreasing corneal neovasculari...

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Autores principales: Landucci, Elisa, Bonomolo, Francesca, De Stefani, Chiara, Mazzantini, Costanza, Pellegrini-Giampietro, Domenico Edoardo, Bilia, Anna Rita, Bergonzi, Maria Camilla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704629/
https://www.ncbi.nlm.nih.gov/pubmed/34959374
http://dx.doi.org/10.3390/pharmaceutics13122093
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author Landucci, Elisa
Bonomolo, Francesca
De Stefani, Chiara
Mazzantini, Costanza
Pellegrini-Giampietro, Domenico Edoardo
Bilia, Anna Rita
Bergonzi, Maria Camilla
author_facet Landucci, Elisa
Bonomolo, Francesca
De Stefani, Chiara
Mazzantini, Costanza
Pellegrini-Giampietro, Domenico Edoardo
Bilia, Anna Rita
Bergonzi, Maria Camilla
author_sort Landucci, Elisa
collection PubMed
description Thymoquinone (TQ) is the main constituent of Nigella sativa L. essential oil. In vitro studies have shown its protective effect against H(2)O(2)-induced oxidative stress in human retinal pigment epithelium cells, and in vivo experiments have demonstrated its effect in decreasing corneal neovascularization and reducing the inflammation in an experimental dry eye model in mice. Its therapeutic use is limited by poor bioavailability, low solubility, and scarce permeability. In this study, two liposomal formulations have been developed, both of which consist of phosphatidylcholine and Plurol Oleique, a liquid lipid, and one of which is coated with 0.1% w/v hyaluronic acid (HA) to increase both TQ solubility and its ocular therapeutic potential. Each formulation has a size <200 nm and an EE% around 70%, determined by scattering techniques and the HPLC-DAD analytical method, respectively, and they result in a 2-fold increase in TQ solubility. HA-coated liposomes are stable over 2 months at +4 °C, and coated and uncoated liposomes present a gradual and prolonged release of TQ. Two cell lines, human corneal epithelial cells (HCEC-2) and human conjunctival epithelial cells (HConEC) were used to investigate the safety of the liposomal formulations. Uptake studies were also performed using fluorescent liposomes. Both liposomes and, in particular, HA-coated liposomes reduce the TQ toxicity observed at high doses in both HCEC-2 and HConEC cells, and both formulations increase the absorption at the cellular level and especially at the nucleus level, with a more pronounced effect for HA-coated liposomes.
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spelling pubmed-87046292021-12-25 Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells Landucci, Elisa Bonomolo, Francesca De Stefani, Chiara Mazzantini, Costanza Pellegrini-Giampietro, Domenico Edoardo Bilia, Anna Rita Bergonzi, Maria Camilla Pharmaceutics Article Thymoquinone (TQ) is the main constituent of Nigella sativa L. essential oil. In vitro studies have shown its protective effect against H(2)O(2)-induced oxidative stress in human retinal pigment epithelium cells, and in vivo experiments have demonstrated its effect in decreasing corneal neovascularization and reducing the inflammation in an experimental dry eye model in mice. Its therapeutic use is limited by poor bioavailability, low solubility, and scarce permeability. In this study, two liposomal formulations have been developed, both of which consist of phosphatidylcholine and Plurol Oleique, a liquid lipid, and one of which is coated with 0.1% w/v hyaluronic acid (HA) to increase both TQ solubility and its ocular therapeutic potential. Each formulation has a size <200 nm and an EE% around 70%, determined by scattering techniques and the HPLC-DAD analytical method, respectively, and they result in a 2-fold increase in TQ solubility. HA-coated liposomes are stable over 2 months at +4 °C, and coated and uncoated liposomes present a gradual and prolonged release of TQ. Two cell lines, human corneal epithelial cells (HCEC-2) and human conjunctival epithelial cells (HConEC) were used to investigate the safety of the liposomal formulations. Uptake studies were also performed using fluorescent liposomes. Both liposomes and, in particular, HA-coated liposomes reduce the TQ toxicity observed at high doses in both HCEC-2 and HConEC cells, and both formulations increase the absorption at the cellular level and especially at the nucleus level, with a more pronounced effect for HA-coated liposomes. MDPI 2021-12-05 /pmc/articles/PMC8704629/ /pubmed/34959374 http://dx.doi.org/10.3390/pharmaceutics13122093 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Landucci, Elisa
Bonomolo, Francesca
De Stefani, Chiara
Mazzantini, Costanza
Pellegrini-Giampietro, Domenico Edoardo
Bilia, Anna Rita
Bergonzi, Maria Camilla
Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells
title Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells
title_full Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells
title_fullStr Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells
title_full_unstemmed Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells
title_short Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells
title_sort preparation of liposomal formulations for ocular delivery of thymoquinone: in vitro evaluation in hcec-2 e hconec cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704629/
https://www.ncbi.nlm.nih.gov/pubmed/34959374
http://dx.doi.org/10.3390/pharmaceutics13122093
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