In Vitro and In Silico Studies of Two 1,4-Naphthoquinones and their Topi- cal Formulation in Bigels

Publication type:
Journal article
Metadata:
Autoren
  • Imen Khelifi
  • Audrey Tourrette
  • Daycem Khelifi
  • Thomas Efferth
  • El Akrem Hayouni
  • Riadh Ksouri
  • Jalloul Bouajila
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000697682900009&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.2174/1567201818666210618111118
eISSN
1875-5704
Externe Identifier
  • Clarivate Analytics Document Solution ID: US8NP
  • PubMed Identifier: 34145994
ISSN
1567-2018
Ausgabe der Veröffentlichung
7
Zeitschrift
CURRENT DRUG DELIVERY
Schlüsselwörter
  • 1,4-Naphthoquinone
  • anti-elastase
  • bigel
  • cytotoxicity
  • drug release
  • molecular docking
Paginierung
931 - 940
Datum der Veröffentlichung
2021
Status
Published
Titel
<i>In Vitro</i> and <i>In Silico</i> Studies of Two 1,4-Naphthoquinones and their Topi- cal Formulation in Bigels
Sub types
  • Article
Ausgabe der Zeitschrift
18

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:sec> <jats:title>Background:</jats:title> <jats:p>1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels are a new technology with great potential, which are designated as drug delivery systems. Biphasic bigels consisting of solid and liquid components represent suitable formulations improving diffusion and bioavailability of NQs into the skin.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p>We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone (M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topical application.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>Molecular docking was performed, and cytotoxicity was evaluated on COLO38 cells using the resazurin assay. M1 and M2 were separately incorporated into bigels consisting of hydrogel organogel with sweet almond oil as the non-polar solvent and span 65 as an organogelator. Their rheological behavior and microscopic properties were characterized. The diffusion kinetics and permeation of 1,4-NQs from bigels were studied by a paddle-over-extraction cell and a “Franz cell” in vitro permeation model.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> Molecular docking data predicted high interactions between elastase and ligands. Hydrogen bonds with LYS233 were observed for M1, M2, and phosphoramidon (positive control). The average binding energies were -8.5 and -9.7 kcal/mol for M1 and M2 and -12.6 kcal/mol for phosphoramidon. M1 and M2 inhibited the elastase activity by 58.9 and 56.6%, respectively. M1 and M2 were cytotoxic towards COLO38 cells (IC<jats:sub>50</jats:sub> value: 2.6 and 9.8 μM). The M1 release from bigels was faster and more efficient than that of M2.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel bigels are efficient and safe formulations to overcome their low bioavailability.</jats:p> </jats:sec>
Autoren
  • Imen Khelifi
  • Audrey Tourrette
  • Daycem Khelifi
  • Thomas Efferth
  • El Akrem Hayouni
  • Riadh Ksouri
  • Jalloul Bouajila
DOI
10.2174/1567201818666210618111118
ISSN
1567-2018
Ausgabe der Veröffentlichung
7
Zeitschrift
Current Drug Delivery
Sprache
en
Paginierung
955 - 964
Datum der Veröffentlichung
2021
Status
Published
Herausgeber
Bentham Science Publishers Ltd.
Herausgeber URL
http://dx.doi.org/10.2174/1567201818666210618111118
Datum der Datenerfassung
2021
Titel
In Vitro and In Silico Studies of Two 1,4-Naphthoquinones and Their Topical Formulation in Bigels
Ausgabe der Zeitschrift
18

Data source: Crossref

Abstract
<h4>Background</h4>1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels are a new technology with great potential, which are designated as drug delivery systems. Biphasic bigels consisting of solid and liquid components represent suitable formulations improving diffusion and bioavailability of NQs into the skin.<h4>Objective</h4>We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone (M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topical application.<h4>Methods</h4>Molecular docking was performed, and cytotoxicity was evaluated on COLO38 cells using the resazurin assay. M1 and M2 were separately incorporated into bigels consisting of hydrogel organogel with sweet almond oil as the non-polar solvent and span 65 as an organogelator. Their rheological behavior and microscopic properties were characterized. The diffusion kinetics and permeation of 1,4-NQs from bigels were studied by a paddle-over-extraction cell and a "Franz cell" in vitro permeation model.<h4>Results</h4>Molecular docking data predicted high interactions between elastase and ligands. Hydrogen bonds with LYS233 were observed for M1, M2, and phosphoramidon (positive control). The average binding energies were -8.5 and -9.7 kcal/mol for M1 and M2 and -12.6 kcal/mol for phosphoramidon. M1 and M2 inhibited the elastase activity by 58.9 and 56.6%, respectively. M1 and M2 were cytotoxic towards COLO38 cells (IC<sub>50</sub> value: 2.6 and 9.8 μM). The M1 release from bigels was faster and more efficient than that of M2.<h4>Conclusion</h4>M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel bigels are efficient and safe formulations to overcome their low bioavailability.
Addresses
  • Laboratory of Aromatic and Medicinal Plants, Center of Biotechnology at the Ecopark of Borj-Cedria, Hammam Lif, Tunisia.
Autoren
  • Imen Khelifi
  • Audrey Tourrette
  • Daycem Khelifi
  • Thomas Efferth
  • El Akrem Hayouni
  • Riadh Ksouri
  • Jalloul Bouajila
DOI
10.2174/1567201818666210618111118
eISSN
1875-5704
Externe Identifier
  • PubMed Identifier: 34145994
Open access
false
ISSN
1567-2018
Ausgabe der Veröffentlichung
7
Zeitschrift
Current drug delivery
Schlüsselwörter
  • Naphthoquinones
  • Hydrogels
  • Drug Delivery Systems
  • Rheology
  • Molecular Docking Simulation
Sprache
eng
Medium
Print
Paginierung
955 - 964
Datum der Veröffentlichung
2021
Status
Published
Datum der Datenerfassung
2021
Titel
In Vitro and In Silico Studies of Two 1,4-Naphthoquinones and Their Topical Formulation in Bigels.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
18

Data source: Europe PubMed Central

Abstract
BACKGROUND: 1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels are a new technology with great potential, which are designated as drug delivery systems. Biphasic bigels consisting of solid and liquid components represent suitable formulations improving diffusion and bioavailability of NQs into the skin. OBJECTIVE: We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone (M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topical application. METHODS: Molecular docking was performed, and cytotoxicity was evaluated on COLO38 cells using the resazurin assay. M1 and M2 were separately incorporated into bigels consisting of hydrogel organogel with sweet almond oil as the non-polar solvent and span 65 as an organogelator. Their rheological behavior and microscopic properties were characterized. The diffusion kinetics and permeation of 1,4-NQs from bigels were studied by a paddle-over-extraction cell and a "Franz cell" in vitro permeation model. RESULTS: Molecular docking data predicted high interactions between elastase and ligands. Hydrogen bonds with LYS233 were observed for M1, M2, and phosphoramidon (positive control). The average binding energies were -8.5 and -9.7 kcal/mol for M1 and M2 and -12.6 kcal/mol for phosphoramidon. M1 and M2 inhibited the elastase activity by 58.9 and 56.6%, respectively. M1 and M2 were cytotoxic towards COLO38 cells (IC50 value: 2.6 and 9.8 μM). The M1 release from bigels was faster and more efficient than that of M2. CONCLUSION: M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel bigels are efficient and safe formulations to overcome their low bioavailability.
Date of acceptance
2021
Autoren
  • Imen Khelifi
  • Audrey Tourrette
  • Daycem Khelifi
  • Thomas Efferth
  • El Akrem Hayouni
  • Riadh Ksouri
  • Jalloul Bouajila
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/34145994
DOI
10.2174/1567201818666210618111118
eISSN
1875-5704
Ausgabe der Veröffentlichung
7
Zeitschrift
Curr Drug Deliv
Schlüsselwörter
  • 1
  • 4-Naphthoquinone
  • anti-elastase
  • bigel
  • cytotoxicity
  • drug release
  • molecular docking.
  • Drug Delivery Systems
  • Hydrogels
  • Molecular Docking Simulation
  • Naphthoquinones
  • Rheology
Sprache
eng
Country
United Arab Emirates
Paginierung
955 - 964
PII
CDD-EPUB-116245
Datum der Veröffentlichung
2021
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Titel
In Vitro and In Silico Studies of Two 1,4-Naphthoquinones and Their Topical Formulation in Bigels.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
18

Data source: PubMed

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