Cyclodextrin Derivatives Conjugated with Aromatic Moieties as pH-responsive Drug Carriers for Anthracycline

Święch, Olga; Dutkiewicz, Paula; Wójciuk, Karolina; Chmurski, Kazimierz; Kruszewski, Marcin; Bilewicz, Renata

doi:10.1021/jp4060632

Cited by 27 publications

(14 citation statements)

References 32 publications

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“…Complexes with βCD and βCDamine are weaker especially in neutral solutions. The stronger βCDLip and βCDGAL, effect is related to the presence of aromatic triazole ring in their structures, which contributes to the strengthening of the complex through proton-acceptor π-π interactions with the aromatic ring of the drug [30]. These results confirm the beneficial effect achieved thanks to appropriate modification of the cyclodextrin.…”

supporting

confidence: 64%

Adjusting the Structure of β-cyclodextrin to Improve Complexation of Anthraquinone-derived Drugs

Krzak¹,

Święch²,

Majdecki³

et al. 2021

Preprint

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β-cyclodextrin (CD) derivatives containing aromatic triazole ring were studied as potential carriers of drugs containing an anthraquinone moiety in the structure: 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 stability constants of the complexes formed and revealed the unique properties of the chosen CDs as effective pH dependent drug complexing agents. The stability constants of the drug complexes with the CDs containing triazole: βCDLip and βCDGAL were significantly larger than with the native βCD. The AQ2CA and AQ2S drugs are ill-soluble and their solubilities increased as the result of complex formation with βCDLip and βCDGAL ligands. AQ2CA, AQ2S were negatively charged at pH 7.4 and therefore they were less prone to form inclusion complex with the hydrophobic CD cavity than at pH 3 (characteristic of gastric juices) when they were protonated. βCDTriazole and βCDGAL ligands were found to form weaker inclusion complexes with the positively charged drug DNR at acidic pH (pH 5.5) than in the neutral medium (pH 7.4) when the drug dissociates to the neutral, uncharged form. This pH dependence is favorable for anti-tumor applications.

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supporting

confidence: 64%

Adjusting the Structure of β-cyclodextrin to Improve Complexation of Anthraquinone-derived Drugs

Krzak¹,

Święch²,

Majdecki³

et al. 2021

Preprint

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“…The solubilities of the βCD derivatives in water decreased with the increase of chain length, hence lipophilicity of the linker connected to the CD ring increased. The solubilities of the derivatives presented here are significantly better than these obtained for similar βCD derivatives but with methoxyphenol group linked by sulfur or triazole group (0.28 mg/ ml or 2.18 mg/ml, respectively) [8,28]. This is due to more hydrophilic character of linkers presented in this paper.…”

Section: Solubility Testsmentioning

confidence: 54%

Monosubstituted hydrazone β-cyclodextrin derivatives for pH-sensitive complex formation with aromatic drugs

Majdecki

Krzak

Żelechowska

et al. 2018

J Incl Phenom Macrocycl Chem

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A new and convenient synthetic pathway was developed to produce monosubstituted cyclodextrins with high yields. Each of the β-cyclodextrin derivatives described in this work has an aromatic substituent connected with cyclodextrin core by a pH-sensitive hydrazone linker and a carbon chain. Carbon chains differ in lengths having one or three carbon atoms. The correlation between water solubility and linker length was determined using UV-Vis spectroscopy, while the dependence of hydrazone bond hydrolysis on the electrolyte pH was confirmed by cyclic voltammetry. The pH-dependent complexformation ability between the hydrazone derivative of cyclodextrin and anthracycline drug was examined by square wave voltammetry. The significantly big solubility and the appropriate pH, at which the hydrolysis of the hydrazone bond occurs, make the newly synthesized derivatives attractive for pharmaceutical and medical applications.

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“…Complexes with βCD and βCDamine were weaker, especially in neutral solutions. The stronger βCDLip and βCDGAL effect is related to the presence of an aromatic triazole ring in their structures, which contributes to the strengthening of the complex through proton-acceptor π–π interactions with the aromatic ring of the drug [ 34 ]. These results confirm the beneficial effect achieved thanks to appropriate modification of the cyclodextrin.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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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. The AQ2CA and AQ2S drugs were poorly soluble, and their solubilities increased as a result of complex formation with βCDLip and βCDGAL ligands. AQ2CA and AQ2S are negatively charged at pH 7.4. Therefore, they were less prone to form an inclusion complex with the hydrophobic CD cavity than at pH 3 (characteristic of gastric juices) when protonated. The βCDTriazole and βCDGAL ligands were found to form weaker inclusion complexes with the positively charged drug DNR at an acidic pH (pH 5.5) than in a neutral medium (pH 7.4) in which the drug dissociates to its neutral, uncharged form. This pH dependence is favorable for antitumor applications.

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Cyclodextrin Derivatives Conjugated with Aromatic Moieties as pH-responsive Drug Carriers for Anthracycline

Cited by 27 publications

References 32 publications

Adjusting the Structure of β-cyclodextrin to Improve Complexation of Anthraquinone-derived Drugs

Adjusting the Structure of β-cyclodextrin to Improve Complexation of Anthraquinone-derived Drugs

Monosubstituted hydrazone β-cyclodextrin derivatives for pH-sensitive complex formation with aromatic drugs

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

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