Cargando…

The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity

One tetracyclic antidepressant, mianserin hydrochloride (MIA), has quite significant side effects on a patients’ health. Cyclodextrins, which are most commonly used to reduce the undesirable features of contained drugs within their hydrophobic interior, also have the potential to alter the toxic beh...

Descripción completa

Detalles Bibliográficos
Autores principales: Belica-Pacha, Sylwia, Małecka, Magdalena, Daśko, Mateusz, Miłowska, Katarzyna, Bryszewska, Maria, Budryn, Grażyna, Oracz, Joanna, Pałecz, Bartłomiej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430726/
https://www.ncbi.nlm.nih.gov/pubmed/34502332
http://dx.doi.org/10.3390/ijms22179419
_version_ 1783750771064438784
author Belica-Pacha, Sylwia
Małecka, Magdalena
Daśko, Mateusz
Miłowska, Katarzyna
Bryszewska, Maria
Budryn, Grażyna
Oracz, Joanna
Pałecz, Bartłomiej
author_facet Belica-Pacha, Sylwia
Małecka, Magdalena
Daśko, Mateusz
Miłowska, Katarzyna
Bryszewska, Maria
Budryn, Grażyna
Oracz, Joanna
Pałecz, Bartłomiej
author_sort Belica-Pacha, Sylwia
collection PubMed
description One tetracyclic antidepressant, mianserin hydrochloride (MIA), has quite significant side effects on a patients’ health. Cyclodextrins, which are most commonly used to reduce the undesirable features of contained drugs within their hydrophobic interior, also have the potential to alter the toxic behavior of the drug. The present paper contains investigations and the characteristics of interaction mechanisms for MIA and the heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) system, and evaluated the effects of the complexation on MIA cytotoxicity. In order to assess whether there was an interaction between MIA and DM-β-CD molecules, isothermal titration calorimetry (ITC) have been chosen. Electrospray ionization mass spectrometry (ESI-MS) helped to establish the complex stoichiometry, and circular dichroism spectroscopy was used to describe the process of complex formation. In order to make a wider interpretative perspective, the molecular docking results have been performed. The viability of Chinese hamster cells were investigated in the presence of DM-β-CD and its complexes with MIA in order to estimate the cytotoxicity of the drug and the conjugate with the chosen cyclodextrin. The viability of B14 cells treated with MIA+DM-β-CD is lower (the toxicity is higher) than with MIA alone, and no protective effects have been observed for complexes of MIA with DM-β-CD in any ratio.
format Online
Article
Text
id pubmed-8430726
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84307262021-09-11 The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity Belica-Pacha, Sylwia Małecka, Magdalena Daśko, Mateusz Miłowska, Katarzyna Bryszewska, Maria Budryn, Grażyna Oracz, Joanna Pałecz, Bartłomiej Int J Mol Sci Article One tetracyclic antidepressant, mianserin hydrochloride (MIA), has quite significant side effects on a patients’ health. Cyclodextrins, which are most commonly used to reduce the undesirable features of contained drugs within their hydrophobic interior, also have the potential to alter the toxic behavior of the drug. The present paper contains investigations and the characteristics of interaction mechanisms for MIA and the heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) system, and evaluated the effects of the complexation on MIA cytotoxicity. In order to assess whether there was an interaction between MIA and DM-β-CD molecules, isothermal titration calorimetry (ITC) have been chosen. Electrospray ionization mass spectrometry (ESI-MS) helped to establish the complex stoichiometry, and circular dichroism spectroscopy was used to describe the process of complex formation. In order to make a wider interpretative perspective, the molecular docking results have been performed. The viability of Chinese hamster cells were investigated in the presence of DM-β-CD and its complexes with MIA in order to estimate the cytotoxicity of the drug and the conjugate with the chosen cyclodextrin. The viability of B14 cells treated with MIA+DM-β-CD is lower (the toxicity is higher) than with MIA alone, and no protective effects have been observed for complexes of MIA with DM-β-CD in any ratio. MDPI 2021-08-30 /pmc/articles/PMC8430726/ /pubmed/34502332 http://dx.doi.org/10.3390/ijms22179419 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
Belica-Pacha, Sylwia
Małecka, Magdalena
Daśko, Mateusz
Miłowska, Katarzyna
Bryszewska, Maria
Budryn, Grażyna
Oracz, Joanna
Pałecz, Bartłomiej
The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity
title The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity
title_full The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity
title_fullStr The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity
title_full_unstemmed The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity
title_short The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity
title_sort interaction of heptakis (2,6-di-o-methyl)-β-cyclodextrin with mianserin hydrochloride and its influence on the drug toxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430726/
https://www.ncbi.nlm.nih.gov/pubmed/34502332
http://dx.doi.org/10.3390/ijms22179419
work_keys_str_mv AT belicapachasylwia theinteractionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT małeckamagdalena theinteractionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT daskomateusz theinteractionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT miłowskakatarzyna theinteractionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT bryszewskamaria theinteractionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT budryngrazyna theinteractionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT oraczjoanna theinteractionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT pałeczbartłomiej theinteractionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT belicapachasylwia interactionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT małeckamagdalena interactionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT daskomateusz interactionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT miłowskakatarzyna interactionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT bryszewskamaria interactionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT budryngrazyna interactionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT oraczjoanna interactionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity
AT pałeczbartłomiej interactionofheptakis26diomethylbcyclodextrinwithmianserinhydrochlorideanditsinfluenceonthedrugtoxicity