Abstract
Mianserin hydrochloride (MIA), a drug, which belongs to a group of tetracyclic, noradrenergic and specific serotonergic antidepressants, is one of the commonly used psychotropic drugs. Despite its important uses and having a number of other potential utilizations, MIA has quite significant side effects on a patient health, including some cytotoxicity. The MIA toxicity could be reduced by drug encapsulation inside a non-toxic carrier, like β-cyclodextrin molecules (β-CD). Cyclodextrins are cone shaped supramolecules with hydrophobic interior, where hydrophobic parts of molecule can be included, and with hydrophilic rims consisting of primary and secondary hydroxyl groups, which can interact with water molecules. This study investigated the characteristic and mechanism for interaction of MIA with β-CD, and evaluated the effects of complexation on MIA cytotoxicity. Chemical shift differences for protons in mianserin hydrochloride and β-cyclodextrin molecules, induced by the formation of the inclusion complexes, have been determined by proton nuclear magnetic resonance spectroscopy. The other chemical properties of mianserin hydrochloride in aqueous solution in the presence of β-cyclodextrin has been examined at 298.15 K with the use of mass spectrometry and circular dichroism. The results showed that interaction of MIA with β-CD occurred through incorporation of MIA aromatic rings inside probably more than one β-CD molecules. The effects of β-cyclodextrin, mianserin hydrochloride and complexes thereof on the viability of Chinese hamster cells were investigated in order to estimate the cytotoxicity of the drug. The viability of B14 cells treated with MIA + β-CD is higher than with MIA and the protective effect is the highest for complexes of MIA:β-CD in a 1:4 ratio.
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