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

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.

Alkalinizing Water-Soluble Local Anesthetic Solutions by Addition of Cyclodextrin

Background and objectivesThe use of sodium bicarbonate for alkalinization of local anesthetics to improve their efficacy has some disadvantages including decreased stability of the solutions. The present study was performed to evaluate usefulness of cyclodextrins (CDs) in improving the solubility and stability of local anesthetic solutions at near physiologic pH without precipitation.MethodsSolubility of local anesthetics with or without CDs in physiologic saline was investigated by monitoring cloudiness or precipitate formation visually and by recording absorbance at 620 nm. Interaction of anesthetic and CD was also studied spectrophotometrically using spectral change of the drugs associated with the inclusion complex formation.ResultsCyclodextrins improved the solubility and stability of the four local anesthetics studied (dibucaine, tetracaine, bupivacaine, and lidocaine). In the neutral pH region, the effects of the CDs were more significant with dibucaine and tetracaine, which are more hydrophobic than the other two. A type of effective CD was different for each anesthetic depending partly on the tendency to form inclusion complex with local anesthetic. The local anesthetic solutions solubilized by CDs were found to remain clear for more than 72 hours without any visible precipitation or turbidity at neutral pHs.ConclusionsThe improved solubility of local anesthetics by adding CD may be caused by inclusion complex formation of CD with local anesthetics. This new preparation for the alkalinized water-soluble anesthetic solutions may be useful for practical application in the clinical setting, although this awaits further study.