Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs.

β-Cyclodextrin (CD) derivatives containing an aromatic triazole ring were studied as potential carriers of the following drugs containing an anthraquinone moiety: anthraquinone-2-sulfonic acid (AQ2S); anthraquinone-2-carboxylic acid (AQ2CA); and a common anthracycline, daunorubicin (DNR). UV-Vis and voltammetry measurements were carried out to determine the solubilities and association constants of the complexes formed, and the results revealed the unique properties of the chosen CDs as effective pH-dependent drug complexing agents. The association constants of the drug complexes with the CDs containing a triazole and lipoic acid (βCDLip) or galactosamine (βCDGAL), were significantly larger than that of the native βCD.

Water-soluble galactosamine derivative of β-cyclodextrin as protective ligand and targeted carrier for delivery of toxic anthracycline drug.

β-cyclodextrin modified with an electron-rich aromatic triazole linker and targeting moiety (galactosamine) was synthesized and studied as a carrier for the anticancer drug, doxorubicin (DOX), with the aim of targeting the pathological cells, reducing the cardiotoxic side effects and increasing the binding of the drug to DNA. The β-cyclodextrins modified with galactosamine (βCDGAL) are non-toxic and highly soluble in aqueous medium compared to the native βCD and βCD modified only with aromatic moiety, such as triazole linker. Molecular modelling and NMR study gave a deeper insight into the ligand structure, providing an explanation for its increased solubility, and the drug-ligand interactions.

Impact of Medium pH on DOX Toxicity toward HeLa and A498 Cell Lines.

The influence of the pH of the multicomponent cell medium on the performance of doxorubicin (DOX), an anticancer drug, was studied on the examples of cervical (HeLa) and kidney (A498) cancer cell lines. The change of pH of the cell medium to more acidic led to a decrease of DOX toxicity on both cell lines due to the change of drug permeability across the cell membrane as a result of drug protonation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) studies and lactate dehydrogenase (LDH) release tests have shown low toxicity of the drug, especially in the case of A498 cells, which are characterized by an extremely high glycolytic metabolism.

Competition between self-inclusion and drug binding explains the pH dependence of the cyclodextrin drug carrier - molecular modelling and electrochemistry studies.

A non-toxic lipoic acid derivative of β cyclodextrin (βCDLip) with an electron-rich aromatic linker was studied as a carrier for the drug doxorubicin with the aim of decreasing the toxic side effects of this drug. The modified cyclodextrin strengthened the drug binding and differentiated the complex-forming ability with dependence on pH. The stability constants of the complexes were evaluated by voltammetry and spectrofluorometry.

Cyclodextrin derivatives conjugated with aromatic moieties as pH-responsive drug carriers for anthracycline.

The modification of cyclodextrins (CDs) with side chains containing aromatic groups was found to lead to an increase of the stability of the complex with the anticancer drug doxorubicin (Dox). The formation constants evaluated by voltammetry were several orders of magnitude larger than that of the unmodified β-CD ligand. For the CDs with aromatic moieties connected by linkers containing a triazole group, the formation constants of the complexes at pH 5.

Intermolecular interactions between doxorubicin and β-cyclodextrin 4-methoxyphenol conjugates.

Newly synthesized derivatives of β-cyclodextrin, mono(6-deoxy-6-(1-1,2,3-triazo-4-yl)-1-propane-3-O-(4-methoxyphenyl))β-cyclodextrin (1) and mono(6-deoxy-6thio(1-propane-3-O-(4-methoxyphenyl))) β-cyclodextrin (2) were designed to be receptors of the anticancer drug doxorubicin, which could potentially decrease the adverse effects of the drug during treatment. In both aqueous and aqueous dimethyl sulfoxide (DMSO) solutions, doxorubicin forms an inclusion complex with the new cyclodextrin derivatives with formation constants of K(s) = 2.3 × 10(4) and K(s) = 3.